Infectious Disease Practitioner

Long COVID continues to be a moving target – continuously evolving and still surprising doctors and patients who have sometimes incapacitating long-term symptoms.

Little about the disorder seems predictable at this point. People can have long COVID after asymptomatic, mild, or severe COVID-19, for example. And when a person gets long COVID – also known as long-haul COVID – symptoms can vary widely.

To address all the uncertainty, the New York State Department of Health gathered experts in primary care, pediatrics, physical medicine, rehabilitation, and pulmonology to answer some pressing questions.

New York in 2020 was the first epicenter of the pandemic in the United States, making it also the center of the long COVID epidemic, says Emily Lutterloh, MD, director of the Division of Epidemiology at the New York State Department of Health.
 

What do you do when you’re seeing a patient with long COVID for the first time?

The first exam varies because there are so many different ways long COVID presents itself, says Benjamin Abramoff, MD, a physical medicine and rehabilitation specialist at Penn Medicine in Philadelphia.

I’ve now been seriously ill with #LongCovid for 11 months. I was never hospitalized. I didn’t even have a “mild” covid case. Instead, I developed Long Covid from an asymptomatic infection.

I’m far from unique. Up to 1/5 of asymptomatic patients go on to have long-term symptoms.

— Ravi Veriah Jacques (@RaviHVJ) February 3, 2022

Assessing their previous and current care also helps to direct their ongoing management, says Zijian Chen, MD, medical director of the Center for Post-COVID Care at Mount Sinai Health System in New York.
 

Can vaccination help people with long COVID?

Anything that we can do to help prevent people from being critically ill or being hospitalized with COVID-19 is helpful to prevent long COVID, says Dr. Abramoff, who is also director of the long COVID clinic at the University of Pennsylvania, Philadelphia.

“So that’s something I always discuss with patients. In some research, sometimes patients do feel better after the vaccine,” he says.
 

What kind of therapies do you find helpful for your patients?

Rehabilitation is a key part of recovery from long COVID, Dr. Abramoff says. “It is very important to make this very patient-specific.”

“We have patients that are working. They’re already going to the gym in some cases but don’t feel like they have the same endurance,” he says. “And then we have patients who are so crippled by their fatigue that they can’t get out of bed.”
 

1/ What is #LongCOVID?!

A disabling malady from ongoing inflammation, autoimmunity, & potential viral reservoirs (GI, brain?)

NEW DATA: The Lungs “light up” on special MRI Scans 3 to 9 months later in patients never hospitalized for COVID.https://t.co/I2kyZ4cK5F pic.twitter.com/dL1P67L2DK

— WesElyMD (@WesElyMD) February 2, 2022

An exercise program can help people who have long COVID.

“There’s a big role for therapy services in the recovery of these patients,” says John Baratta, MD, of the department of physical medicine and rehabilitation at the University of North Carolina at Chapel Hill.

But the limited number of long COVID clinics can mean some people are unable to get to therapists trained on the needs of patients with lingering COVID symptoms. Educating community physical and occupational therapists is one solution.
 

How long does it take for people with long COVID to recover and get back to 100% if they can?

Specific numbers aren’t really available, Dr. Baratta says.

“But I can tell you the general trend that I see is that a lot of patients have a gradual improvement of symptoms. The slow but steady improvement with time may be the body’s natural healing process, a result of medical interventions, or both.”

It can help to reassure people with long COVID that they will not be discharged from care until they feel they’ve maximized their health, says Sharagim Kemp, DO, medical director of the COVID Recovery Program for Nuvance Health, a health system in New York and Connecticut.

It’s essential to set realistic recovery expectations and tell patients that not everyone will return to 100% of their pre-COVID functioning, she says.

“Once we are able to help them reset their expectations, there’s almost an accelerated recovery because they are not putting that pressure on themselves anymore,” Dr. Kemp says.
 

What are the most common symptoms you’re seeing in long COVID?

It’s helpful to think of long COVID as a very broad umbrella term, Dr. Abramoff says.

Echoing what many others have observed, fatigue, cognitive dysfunction or “brain fog,“ and shortness of breath or troubled breathing appear to be the most common symptoms, he says.

Some reported vague symptoms, Dr. Kemp says.

People may go to the doctor “not even realizing that they had COVID. That’s one of the important points here – to have a high index of suspicion for patients who come in with multiple symptoms,” she says.

For this reason, patients can report symptoms that don’t necessarily fit into any specialty, says Sarah J. Ryan, MD, an internal medicine doctor at Columbia University Irving Medical Center in New York. People say they are “just not themselves” or they are tired after their COVID-19 recovery.
 

Is there a connection between severe COVID cases and severe long COVID?

“It’s not like that at all. I would say that more than 80% of the patients that we see had mild to moderate illness and they were not hospitalized,” Dr. Baratta says.

Long COVID is a bit different in children and teenagers, says Ixsy Ramirez, MD, a pediatric pulmonologist at University of Michigan Health, Ann Arbor. Most patients in the long COVID clinic at the University of Michigan were previously healthy, and not children with asthma or other lung conditions as one might expect. In fact, many are student athletes, or were before they had long COVID.

In this population, shortness of breath is most common, followed by chest pain and fatigue. Unfortunately, the symptoms are so serious for many kids that their performance is limited, even if they can return to competitive play.
 

Are there defined criteria you use to diagnose long COVID? How do you give someone a diagnosis?

That’s an ever-evolving question, Dr. Kemp says. The generally accepted definition centers on persistent or new symptoms 4 weeks or more after the original COVID-19 illness, but there are exceptions.

Researchers are working on lab tests to help confirm the diagnosis. But without a definitive blood biomarker, getting to the diagnosis requires “some thorough detective work,” Dr. Ryan says.
 

Do you bring in mental health providers to help with treatment?

“We focus on mental health quite a bit actually,” says, Dr. Chen, cofounder of his institution’s COVID recovery clinic. Mount Sinai offers one-on-one and group mental health services, for example.

“Personally, I’ve seen patients that I did not expect to have such severe mental health changes” with long COVID.
 

One of the most powerful accounts and testimonies I have seen on what most #LongCovid patients experience when interacting with their doctors.

“I did not fit in a box, so they chose not to see me, even worse they made me feel like it was my fault for not fitting in their box” pic.twitter.com/7GQLBucuO5

— charlos (@loscharlos) February 3, 2022

Examples include severe depression, cases of acute psychosis, hallucinations, and other problems “that are really unexpected after a viral illness.”

Stony Brook University Hospital in New York has a long COVID clinic staffed by multiple primary care doctors who do exams and refer patients to services. A bonus of offering psychological services to all post-COVID patients is doctors get a more complete picture of each person and a better understanding of what they are going through, says Abigail Chua, MD, a pulmonologist at Stony Brook.

Some empathy is essential, Dr. Baratta says. “It’s important to recognize that a lot of these patients present with a sense of grief or loss for their prior life.”
 

What does the future hold?

A simple test to diagnose long COVID, combined with an effective treatment that helps people feel better within a week, would be ideal, Dr. Abramoff says.

“That would be lovely. But you know, we’re just not at that point.”

And it would be helpful to start identifying subtypes of long COVID so diagnosis and treatment can be more targeted, Dr. Abramoff says. Otherwise, “It’s going to be a very challenging approach to try to treat all of our patients with long COVID symptoms the same way.”

Good clinical trials likewise are needed to address all the subtleties of long COVID.

A number of long COVID centers are collaborating on research to find out more, Dr. Chen says. Actions include setting up a bank of tissue samples from people with long COVID so researchers can continue to figure out the condition.

One goal, Dr. Chen says, would be the ability to treat long COVID rather than just its symptoms.

Long COVID emphasizes the need to prevent people from getting COVID in the first place, Dr. Ramirez says. This will continue to be important, particularly when some people dismiss the seriousness of COVID, comparing it to a cold if they get it. That attitude discounts the large number of people who unfortunately go on to develop long-term, often debilitating, symptoms.

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

Long COVID continues to be a moving target – continuously evolving and still surprising doctors and patients who have sometimes incapacitating long-term symptoms.

Little about the disorder seems predictable at this point. People can have long COVID after asymptomatic, mild, or severe COVID-19, for example. And when a person gets long COVID – also known as long-haul COVID – symptoms can vary widely.

To address all the uncertainty, the New York State Department of Health gathered experts in primary care, pediatrics, physical medicine, rehabilitation, and pulmonology to answer some pressing questions.

New York in 2020 was the first epicenter of the pandemic in the United States, making it also the center of the long COVID epidemic, says Emily Lutterloh, MD, director of the Division of Epidemiology at the New York State Department of Health.
 

What do you do when you’re seeing a patient with long COVID for the first time?

The first exam varies because there are so many different ways long COVID presents itself, says Benjamin Abramoff, MD, a physical medicine and rehabilitation specialist at Penn Medicine in Philadelphia.

I’ve now been seriously ill with #LongCovid for 11 months. I was never hospitalized. I didn’t even have a “mild” covid case. Instead, I developed Long Covid from an asymptomatic infection.

I’m far from unique. Up to 1/5 of asymptomatic patients go on to have long-term symptoms.

— Ravi Veriah Jacques (@RaviHVJ) February 3, 2022

Assessing their previous and current care also helps to direct their ongoing management, says Zijian Chen, MD, medical director of the Center for Post-COVID Care at Mount Sinai Health System in New York.
 

Can vaccination help people with long COVID?

Anything that we can do to help prevent people from being critically ill or being hospitalized with COVID-19 is helpful to prevent long COVID, says Dr. Abramoff, who is also director of the long COVID clinic at the University of Pennsylvania, Philadelphia.

“So that’s something I always discuss with patients. In some research, sometimes patients do feel better after the vaccine,” he says.
 

What kind of therapies do you find helpful for your patients?

Rehabilitation is a key part of recovery from long COVID, Dr. Abramoff says. “It is very important to make this very patient-specific.”

“We have patients that are working. They’re already going to the gym in some cases but don’t feel like they have the same endurance,” he says. “And then we have patients who are so crippled by their fatigue that they can’t get out of bed.”
 

1/ What is #LongCOVID?!

A disabling malady from ongoing inflammation, autoimmunity, & potential viral reservoirs (GI, brain?)

NEW DATA: The Lungs “light up” on special MRI Scans 3 to 9 months later in patients never hospitalized for COVID.https://t.co/I2kyZ4cK5F pic.twitter.com/dL1P67L2DK

— WesElyMD (@WesElyMD) February 2, 2022

An exercise program can help people who have long COVID.

“There’s a big role for therapy services in the recovery of these patients,” says John Baratta, MD, of the department of physical medicine and rehabilitation at the University of North Carolina at Chapel Hill.

But the limited number of long COVID clinics can mean some people are unable to get to therapists trained on the needs of patients with lingering COVID symptoms. Educating community physical and occupational therapists is one solution.
 

How long does it take for people with long COVID to recover and get back to 100% if they can?

Specific numbers aren’t really available, Dr. Baratta says.

“But I can tell you the general trend that I see is that a lot of patients have a gradual improvement of symptoms. The slow but steady improvement with time may be the body’s natural healing process, a result of medical interventions, or both.”

It can help to reassure people with long COVID that they will not be discharged from care until they feel they’ve maximized their health, says Sharagim Kemp, DO, medical director of the COVID Recovery Program for Nuvance Health, a health system in New York and Connecticut.

It’s essential to set realistic recovery expectations and tell patients that not everyone will return to 100% of their pre-COVID functioning, she says.

“Once we are able to help them reset their expectations, there’s almost an accelerated recovery because they are not putting that pressure on themselves anymore,” Dr. Kemp says.
 

What are the most common symptoms you’re seeing in long COVID?

It’s helpful to think of long COVID as a very broad umbrella term, Dr. Abramoff says.

Echoing what many others have observed, fatigue, cognitive dysfunction or “brain fog,“ and shortness of breath or troubled breathing appear to be the most common symptoms, he says.

Some reported vague symptoms, Dr. Kemp says.

People may go to the doctor “not even realizing that they had COVID. That’s one of the important points here – to have a high index of suspicion for patients who come in with multiple symptoms,” she says.

For this reason, patients can report symptoms that don’t necessarily fit into any specialty, says Sarah J. Ryan, MD, an internal medicine doctor at Columbia University Irving Medical Center in New York. People say they are “just not themselves” or they are tired after their COVID-19 recovery.
 

Is there a connection between severe COVID cases and severe long COVID?

“It’s not like that at all. I would say that more than 80% of the patients that we see had mild to moderate illness and they were not hospitalized,” Dr. Baratta says.

Long COVID is a bit different in children and teenagers, says Ixsy Ramirez, MD, a pediatric pulmonologist at University of Michigan Health, Ann Arbor. Most patients in the long COVID clinic at the University of Michigan were previously healthy, and not children with asthma or other lung conditions as one might expect. In fact, many are student athletes, or were before they had long COVID.

In this population, shortness of breath is most common, followed by chest pain and fatigue. Unfortunately, the symptoms are so serious for many kids that their performance is limited, even if they can return to competitive play.
 

Are there defined criteria you use to diagnose long COVID? How do you give someone a diagnosis?

That’s an ever-evolving question, Dr. Kemp says. The generally accepted definition centers on persistent or new symptoms 4 weeks or more after the original COVID-19 illness, but there are exceptions.

Researchers are working on lab tests to help confirm the diagnosis. But without a definitive blood biomarker, getting to the diagnosis requires “some thorough detective work,” Dr. Ryan says.
 

Do you bring in mental health providers to help with treatment?

“We focus on mental health quite a bit actually,” says, Dr. Chen, cofounder of his institution’s COVID recovery clinic. Mount Sinai offers one-on-one and group mental health services, for example.

“Personally, I’ve seen patients that I did not expect to have such severe mental health changes” with long COVID.
 

One of the most powerful accounts and testimonies I have seen on what most #LongCovid patients experience when interacting with their doctors.

“I did not fit in a box, so they chose not to see me, even worse they made me feel like it was my fault for not fitting in their box” pic.twitter.com/7GQLBucuO5

— charlos (@loscharlos) February 3, 2022

Examples include severe depression, cases of acute psychosis, hallucinations, and other problems “that are really unexpected after a viral illness.”

Stony Brook University Hospital in New York has a long COVID clinic staffed by multiple primary care doctors who do exams and refer patients to services. A bonus of offering psychological services to all post-COVID patients is doctors get a more complete picture of each person and a better understanding of what they are going through, says Abigail Chua, MD, a pulmonologist at Stony Brook.

Some empathy is essential, Dr. Baratta says. “It’s important to recognize that a lot of these patients present with a sense of grief or loss for their prior life.”
 

What does the future hold?

A simple test to diagnose long COVID, combined with an effective treatment that helps people feel better within a week, would be ideal, Dr. Abramoff says.

“That would be lovely. But you know, we’re just not at that point.”

And it would be helpful to start identifying subtypes of long COVID so diagnosis and treatment can be more targeted, Dr. Abramoff says. Otherwise, “It’s going to be a very challenging approach to try to treat all of our patients with long COVID symptoms the same way.”

Good clinical trials likewise are needed to address all the subtleties of long COVID.

A number of long COVID centers are collaborating on research to find out more, Dr. Chen says. Actions include setting up a bank of tissue samples from people with long COVID so researchers can continue to figure out the condition.

One goal, Dr. Chen says, would be the ability to treat long COVID rather than just its symptoms.

Long COVID emphasizes the need to prevent people from getting COVID in the first place, Dr. Ramirez says. This will continue to be important, particularly when some people dismiss the seriousness of COVID, comparing it to a cold if they get it. That attitude discounts the large number of people who unfortunately go on to develop long-term, often debilitating, symptoms.

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

Long COVID continues to be a moving target – continuously evolving and still surprising doctors and patients who have sometimes incapacitating long-term symptoms.

Little about the disorder seems predictable at this point. People can have long COVID after asymptomatic, mild, or severe COVID-19, for example. And when a person gets long COVID – also known as long-haul COVID – symptoms can vary widely.

To address all the uncertainty, the New York State Department of Health gathered experts in primary care, pediatrics, physical medicine, rehabilitation, and pulmonology to answer some pressing questions.

New York in 2020 was the first epicenter of the pandemic in the United States, making it also the center of the long COVID epidemic, says Emily Lutterloh, MD, director of the Division of Epidemiology at the New York State Department of Health.
 

What do you do when you’re seeing a patient with long COVID for the first time?

The first exam varies because there are so many different ways long COVID presents itself, says Benjamin Abramoff, MD, a physical medicine and rehabilitation specialist at Penn Medicine in Philadelphia.

I’ve now been seriously ill with #LongCovid for 11 months. I was never hospitalized. I didn’t even have a “mild” covid case. Instead, I developed Long Covid from an asymptomatic infection.

I’m far from unique. Up to 1/5 of asymptomatic patients go on to have long-term symptoms.

— Ravi Veriah Jacques (@RaviHVJ) February 3, 2022

Assessing their previous and current care also helps to direct their ongoing management, says Zijian Chen, MD, medical director of the Center for Post-COVID Care at Mount Sinai Health System in New York.
 

Can vaccination help people with long COVID?

Anything that we can do to help prevent people from being critically ill or being hospitalized with COVID-19 is helpful to prevent long COVID, says Dr. Abramoff, who is also director of the long COVID clinic at the University of Pennsylvania, Philadelphia.

“So that’s something I always discuss with patients. In some research, sometimes patients do feel better after the vaccine,” he says.
 

What kind of therapies do you find helpful for your patients?

Rehabilitation is a key part of recovery from long COVID, Dr. Abramoff says. “It is very important to make this very patient-specific.”

“We have patients that are working. They’re already going to the gym in some cases but don’t feel like they have the same endurance,” he says. “And then we have patients who are so crippled by their fatigue that they can’t get out of bed.”
 

1/ What is #LongCOVID?!

A disabling malady from ongoing inflammation, autoimmunity, & potential viral reservoirs (GI, brain?)

NEW DATA: The Lungs “light up” on special MRI Scans 3 to 9 months later in patients never hospitalized for COVID.https://t.co/I2kyZ4cK5F pic.twitter.com/dL1P67L2DK

— WesElyMD (@WesElyMD) February 2, 2022

An exercise program can help people who have long COVID.

“There’s a big role for therapy services in the recovery of these patients,” says John Baratta, MD, of the department of physical medicine and rehabilitation at the University of North Carolina at Chapel Hill.

But the limited number of long COVID clinics can mean some people are unable to get to therapists trained on the needs of patients with lingering COVID symptoms. Educating community physical and occupational therapists is one solution.
 

How long does it take for people with long COVID to recover and get back to 100% if they can?

Specific numbers aren’t really available, Dr. Baratta says.

“But I can tell you the general trend that I see is that a lot of patients have a gradual improvement of symptoms. The slow but steady improvement with time may be the body’s natural healing process, a result of medical interventions, or both.”

It can help to reassure people with long COVID that they will not be discharged from care until they feel they’ve maximized their health, says Sharagim Kemp, DO, medical director of the COVID Recovery Program for Nuvance Health, a health system in New York and Connecticut.

It’s essential to set realistic recovery expectations and tell patients that not everyone will return to 100% of their pre-COVID functioning, she says.

“Once we are able to help them reset their expectations, there’s almost an accelerated recovery because they are not putting that pressure on themselves anymore,” Dr. Kemp says.
 

What are the most common symptoms you’re seeing in long COVID?

It’s helpful to think of long COVID as a very broad umbrella term, Dr. Abramoff says.

Echoing what many others have observed, fatigue, cognitive dysfunction or “brain fog,“ and shortness of breath or troubled breathing appear to be the most common symptoms, he says.

Some reported vague symptoms, Dr. Kemp says.

People may go to the doctor “not even realizing that they had COVID. That’s one of the important points here – to have a high index of suspicion for patients who come in with multiple symptoms,” she says.

For this reason, patients can report symptoms that don’t necessarily fit into any specialty, says Sarah J. Ryan, MD, an internal medicine doctor at Columbia University Irving Medical Center in New York. People say they are “just not themselves” or they are tired after their COVID-19 recovery.
 

Is there a connection between severe COVID cases and severe long COVID?

“It’s not like that at all. I would say that more than 80% of the patients that we see had mild to moderate illness and they were not hospitalized,” Dr. Baratta says.

Long COVID is a bit different in children and teenagers, says Ixsy Ramirez, MD, a pediatric pulmonologist at University of Michigan Health, Ann Arbor. Most patients in the long COVID clinic at the University of Michigan were previously healthy, and not children with asthma or other lung conditions as one might expect. In fact, many are student athletes, or were before they had long COVID.

In this population, shortness of breath is most common, followed by chest pain and fatigue. Unfortunately, the symptoms are so serious for many kids that their performance is limited, even if they can return to competitive play.
 

Are there defined criteria you use to diagnose long COVID? How do you give someone a diagnosis?

That’s an ever-evolving question, Dr. Kemp says. The generally accepted definition centers on persistent or new symptoms 4 weeks or more after the original COVID-19 illness, but there are exceptions.

Researchers are working on lab tests to help confirm the diagnosis. But without a definitive blood biomarker, getting to the diagnosis requires “some thorough detective work,” Dr. Ryan says.
 

Do you bring in mental health providers to help with treatment?

“We focus on mental health quite a bit actually,” says, Dr. Chen, cofounder of his institution’s COVID recovery clinic. Mount Sinai offers one-on-one and group mental health services, for example.

“Personally, I’ve seen patients that I did not expect to have such severe mental health changes” with long COVID.
 

One of the most powerful accounts and testimonies I have seen on what most #LongCovid patients experience when interacting with their doctors.

“I did not fit in a box, so they chose not to see me, even worse they made me feel like it was my fault for not fitting in their box” pic.twitter.com/7GQLBucuO5

— charlos (@loscharlos) February 3, 2022

Examples include severe depression, cases of acute psychosis, hallucinations, and other problems “that are really unexpected after a viral illness.”

Stony Brook University Hospital in New York has a long COVID clinic staffed by multiple primary care doctors who do exams and refer patients to services. A bonus of offering psychological services to all post-COVID patients is doctors get a more complete picture of each person and a better understanding of what they are going through, says Abigail Chua, MD, a pulmonologist at Stony Brook.

Some empathy is essential, Dr. Baratta says. “It’s important to recognize that a lot of these patients present with a sense of grief or loss for their prior life.”
 

What does the future hold?

A simple test to diagnose long COVID, combined with an effective treatment that helps people feel better within a week, would be ideal, Dr. Abramoff says.

“That would be lovely. But you know, we’re just not at that point.”

And it would be helpful to start identifying subtypes of long COVID so diagnosis and treatment can be more targeted, Dr. Abramoff says. Otherwise, “It’s going to be a very challenging approach to try to treat all of our patients with long COVID symptoms the same way.”

Good clinical trials likewise are needed to address all the subtleties of long COVID.

A number of long COVID centers are collaborating on research to find out more, Dr. Chen says. Actions include setting up a bank of tissue samples from people with long COVID so researchers can continue to figure out the condition.

One goal, Dr. Chen says, would be the ability to treat long COVID rather than just its symptoms.

Long COVID emphasizes the need to prevent people from getting COVID in the first place, Dr. Ramirez says. This will continue to be important, particularly when some people dismiss the seriousness of COVID, comparing it to a cold if they get it. That attitude discounts the large number of people who unfortunately go on to develop long-term, often debilitating, symptoms.

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

A new, highly-virulent form of the HIV-1 virus has been discovered in the Netherlands by an international collaboration led by researchers at the University of Oxford’s Big Data Institute.

In a study published in the journal Science, researchers identified a VB variant (virulent subtype B) of HIV-1 linked to higher viral loads, increased transmissibility, and a faster decline in CD4 cell levels, leading to increased immune deficiency.

In light of the ongoing pandemic and current focus on SARS-CoV-19 virus variants such as Delta or Omicron, the discovery provides a salutary reminder that other viral pathogens, including those responsible for many long-standing endemic diseases, undergo a similar process of mutation.

Lead author Dr. Chris Wymant said: “Before this study, the genetics of the HIV virus were known to be relevant for virulence, implying that the evolution of a new variant could change its impact on health. Discovery of the VB variant demonstrated this, providing a rare example of the risk posed by viral virulence evolution.”
 

Global disease, local variants

Human immunodeficiency virus (HIV) infections affect around 38 million people worldwide, with more than half a million  people dying from AIDS-related illnesses each year. The disease-causing retroviruses, of which the HIV-1 virus is most common, destroy CD4+ T cells, causing immune deficiency and leading eventually to AIDS.

RNA viruses such as HIV-1 have long been a particular concern to scientists because their error-prone replication, lacking the error-correcting mechanisms of DNA, results in more spontaneous mutations and so a higher potential for acquiring new characteristics.

The VB variant of HIV-1 was first detected in samples from 2,461 HIV-positive people whose viral genomes were sequenced as part of the ongoing BEEHIVE project. Within this cohort, researchers identified 17 people with very highly elevated viral loads.

As 15 of these individuals came from the Netherlands, the researchers next examined virus gene data from 6,706 HIV-positive patients in a Dutch HIV cohort study (ATHENA), identifying a further 92 people carrying the same VB variant.

By analysing patterns of genetic variation in the samples, researchers estimated that the VB variant first emerged in the Netherlands in the late 1990s, occurring through de novo mutations rather than recombination. It spread more quickly than other HIV variants initially, but cases have been declining since around 2010, most likely due to the availability of more effective combination anti-retroviral treatments.
 

Increased virulence

The researchers found a number of differences in people infected with the VB variant compared with those infected by other HIV variants. Prior to starting anti-retroviral treatment, individuals with the VB variant were found to have:

Around a 3.5- to 5.5-fold increase in viral load (a marker for viral virulence)

Double the rate of CD4 cell decline compared with individuals with other subtype-B strains, even after adjusting for viral load

Increased risk of transmitting the virus (the study used the virus ‘local branching index’ as a proxy for transmissibility).

Reassuringly, after starting anti-retroviral treatment, individuals with the VB variant showed similar CD4 cell recovery and survival to individuals with other HIV variants. However, the authors emphasise that due of the more rapid decline in immune function with the VB variant, it is critical to identify VB-positive individuals early and start treatment promptly.

Senior author Professor Christophe Fraser explained: “Our findings emphasise the importance of World Health Organization guidance that individuals at risk of acquiring HIV have access to regular testing to allow early diagnosis, followed by immediate treatment.

“This limits the amount of time HIV can damage an individual’s immune system and jeopardise their health. It also ensures that HIV is suppressed as quickly as possible, which prevents transmission to other individuals.”

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

A new, highly-virulent form of the HIV-1 virus has been discovered in the Netherlands by an international collaboration led by researchers at the University of Oxford’s Big Data Institute.

In a study published in the journal Science, researchers identified a VB variant (virulent subtype B) of HIV-1 linked to higher viral loads, increased transmissibility, and a faster decline in CD4 cell levels, leading to increased immune deficiency.

In light of the ongoing pandemic and current focus on SARS-CoV-19 virus variants such as Delta or Omicron, the discovery provides a salutary reminder that other viral pathogens, including those responsible for many long-standing endemic diseases, undergo a similar process of mutation.

Lead author Dr. Chris Wymant said: “Before this study, the genetics of the HIV virus were known to be relevant for virulence, implying that the evolution of a new variant could change its impact on health. Discovery of the VB variant demonstrated this, providing a rare example of the risk posed by viral virulence evolution.”
 

Global disease, local variants

Human immunodeficiency virus (HIV) infections affect around 38 million people worldwide, with more than half a million  people dying from AIDS-related illnesses each year. The disease-causing retroviruses, of which the HIV-1 virus is most common, destroy CD4+ T cells, causing immune deficiency and leading eventually to AIDS.

RNA viruses such as HIV-1 have long been a particular concern to scientists because their error-prone replication, lacking the error-correcting mechanisms of DNA, results in more spontaneous mutations and so a higher potential for acquiring new characteristics.

The VB variant of HIV-1 was first detected in samples from 2,461 HIV-positive people whose viral genomes were sequenced as part of the ongoing BEEHIVE project. Within this cohort, researchers identified 17 people with very highly elevated viral loads.

As 15 of these individuals came from the Netherlands, the researchers next examined virus gene data from 6,706 HIV-positive patients in a Dutch HIV cohort study (ATHENA), identifying a further 92 people carrying the same VB variant.

By analysing patterns of genetic variation in the samples, researchers estimated that the VB variant first emerged in the Netherlands in the late 1990s, occurring through de novo mutations rather than recombination. It spread more quickly than other HIV variants initially, but cases have been declining since around 2010, most likely due to the availability of more effective combination anti-retroviral treatments.
 

Increased virulence

The researchers found a number of differences in people infected with the VB variant compared with those infected by other HIV variants. Prior to starting anti-retroviral treatment, individuals with the VB variant were found to have:

Around a 3.5- to 5.5-fold increase in viral load (a marker for viral virulence)

Double the rate of CD4 cell decline compared with individuals with other subtype-B strains, even after adjusting for viral load

Increased risk of transmitting the virus (the study used the virus ‘local branching index’ as a proxy for transmissibility).

Reassuringly, after starting anti-retroviral treatment, individuals with the VB variant showed similar CD4 cell recovery and survival to individuals with other HIV variants. However, the authors emphasise that due of the more rapid decline in immune function with the VB variant, it is critical to identify VB-positive individuals early and start treatment promptly.

Senior author Professor Christophe Fraser explained: “Our findings emphasise the importance of World Health Organization guidance that individuals at risk of acquiring HIV have access to regular testing to allow early diagnosis, followed by immediate treatment.

“This limits the amount of time HIV can damage an individual’s immune system and jeopardise their health. It also ensures that HIV is suppressed as quickly as possible, which prevents transmission to other individuals.”

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

A new, highly-virulent form of the HIV-1 virus has been discovered in the Netherlands by an international collaboration led by researchers at the University of Oxford’s Big Data Institute.

In a study published in the journal Science, researchers identified a VB variant (virulent subtype B) of HIV-1 linked to higher viral loads, increased transmissibility, and a faster decline in CD4 cell levels, leading to increased immune deficiency.

In light of the ongoing pandemic and current focus on SARS-CoV-19 virus variants such as Delta or Omicron, the discovery provides a salutary reminder that other viral pathogens, including those responsible for many long-standing endemic diseases, undergo a similar process of mutation.

Lead author Dr. Chris Wymant said: “Before this study, the genetics of the HIV virus were known to be relevant for virulence, implying that the evolution of a new variant could change its impact on health. Discovery of the VB variant demonstrated this, providing a rare example of the risk posed by viral virulence evolution.”
 

Global disease, local variants

Human immunodeficiency virus (HIV) infections affect around 38 million people worldwide, with more than half a million  people dying from AIDS-related illnesses each year. The disease-causing retroviruses, of which the HIV-1 virus is most common, destroy CD4+ T cells, causing immune deficiency and leading eventually to AIDS.

RNA viruses such as HIV-1 have long been a particular concern to scientists because their error-prone replication, lacking the error-correcting mechanisms of DNA, results in more spontaneous mutations and so a higher potential for acquiring new characteristics.

The VB variant of HIV-1 was first detected in samples from 2,461 HIV-positive people whose viral genomes were sequenced as part of the ongoing BEEHIVE project. Within this cohort, researchers identified 17 people with very highly elevated viral loads.

As 15 of these individuals came from the Netherlands, the researchers next examined virus gene data from 6,706 HIV-positive patients in a Dutch HIV cohort study (ATHENA), identifying a further 92 people carrying the same VB variant.

By analysing patterns of genetic variation in the samples, researchers estimated that the VB variant first emerged in the Netherlands in the late 1990s, occurring through de novo mutations rather than recombination. It spread more quickly than other HIV variants initially, but cases have been declining since around 2010, most likely due to the availability of more effective combination anti-retroviral treatments.
 

Increased virulence

The researchers found a number of differences in people infected with the VB variant compared with those infected by other HIV variants. Prior to starting anti-retroviral treatment, individuals with the VB variant were found to have:

Around a 3.5- to 5.5-fold increase in viral load (a marker for viral virulence)

Double the rate of CD4 cell decline compared with individuals with other subtype-B strains, even after adjusting for viral load

Increased risk of transmitting the virus (the study used the virus ‘local branching index’ as a proxy for transmissibility).

Reassuringly, after starting anti-retroviral treatment, individuals with the VB variant showed similar CD4 cell recovery and survival to individuals with other HIV variants. However, the authors emphasise that due of the more rapid decline in immune function with the VB variant, it is critical to identify VB-positive individuals early and start treatment promptly.

Senior author Professor Christophe Fraser explained: “Our findings emphasise the importance of World Health Organization guidance that individuals at risk of acquiring HIV have access to regular testing to allow early diagnosis, followed by immediate treatment.

“This limits the amount of time HIV can damage an individual’s immune system and jeopardise their health. It also ensures that HIV is suppressed as quickly as possible, which prevents transmission to other individuals.”

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

Samples from patients in the United States and Kenya show an increasing emergence of previously undetected vancomycin-resistant strains of Clostridioides difficile, sparking concern as recurrences in the treatment of C. difficile infection (CDI) continue to rise.

“Our results may help explain a decreasing effectiveness of antibiotic-based therapy in C. difficile infection, since a significant proportion of patients harboring strains with reduced susceptibility to vancomycin may not respond to treatment,” reported the authors in research published recently in Clinical Infectious Diseases.

The spread of the resistant strains “has serious public health implications, underscoring an urgent need for a comprehensive analysis of the circulating strains to help inform clinical decisions,” they added.

Commenting on the findings, Cornelius J. Clancy, MD, professor of medicine at the University of Pittsburgh, and chief of infectious diseases at the Veterans Affairs Pittsburgh Healthcare System, echoed the concern.

“The casual belief has been that [C. difficile] strains at most centers can be assumed to be vancomycin susceptible,” he told this news organization. “This study shows that this assumption can no longer be taken as a given.”

Dr. Clancy, who was not involved with this research, noted that “based on this study, there might be need for the Infectious Diseases Society of America and other organizations to offer guidance on generating good, quality surveillance data for C. difficile resistance.”

With C. difficile showing the ability to resist multiple antibiotics, drugs in the armamentarium to treat the infection have declined in recent years, and recurrences with the infection are reported in up to 25% of cases.

Oral vancomycin is recommended as the antibiotic of choice by the IDSA and the Society for Healthcare Epidemiology of America for severe as well as nonsevere cases of CDI, and although there are reports of nine vancomycin-resistant gene clusters, most involve Enterococcus.

To take a closer look at the prevalence of vancomycin-resistant C. difficile strains, first author Charles Darkoh, PhD, with the Center for Infectious Diseases at the University of Texas Health Science Center, Houston, and colleagues analyzed stool samples from patients with CDI, including 438 patients in Houston, taken between 2012 and 2017, and 98 in Nairobi, Kenya, taken in 2017.

They found that, among samples from patients in Houston, over the time period, 26% showed vancomycin nonsusceptible C. difficile isolates and 29% had isolates that were metronidazole resistant.

And among samples from the Nairobi patients, 67% harbored vancomycin-resistant isolates and 85% had isolates resistant to metronidazole.

Of note, the proportion of samples containing vancomycin-resistant C. difficile in the Houston patients showed a marked increase over time, from «complete absence» in 2012 to approximately 35% in 2017, the authors reported.

“These nonsusceptibility rates significantly exceeded prior reports from other studies conducted in the United States and Europe from 2011 to 2014, suggesting a lower percentage of resistance to both metronidazole and vancomycin,” the authors wrote.

Further experiments on mouse models infected with one of the vancomycin-resistant isolates showed that treatment with vancomycin failed to eradicate the infection, and 5-day survival was significantly lower after vancomycin treatment in those mice (25%) versus those infected with strains known to be vancomycin sensitive (50%).
 

Unrecognized genetic strains

Whole-genome sequencing of 10 of the resistant isolates showed no matches with gene clusters that have been previously recognized as being vancomycin resistant, suggesting the emergence of new clusters.

“Together, these results suggest unknown genetic elements associated with vancomycin nonsusceptibility in isolates circulating in the patient population,” the authors wrote.

Dr. Darkoh told this news organization that the research team is currently working to further investigate the patterns and mechanisms.

“We are currently working on a follow-up study for the next 5 years to find out how widespread this is,” he said. “We want to make sure it’s not necessarily just occurring in the settings we studied, and we also need to establish the mechanism of resistance.”

Further commenting on the results, Dr. Clancy noted that “the extent of resistance caught many in the field a bit off guard, as they are higher than previously reported.”

“The data are also concerning because most centers do not routinely test C. difficile for drug susceptibility.”

Dr. Clancy noted that “another immediately pressing need is to understand mechanisms of resistance. It was quite striking that vancomycin-resistant strains in this study did not carry vanA genes, pointing to previously unrecognized mechanisms of resistance.”

“As is often the case, antibiotic overuse was likely a factor in the resistances, with overtesting often leading to overtreatment of C. difficile,” Dr. Clancy said. “The situation may have been compounded by failure to appreciate how entrenched C. difficile resistance may be at certain hospitals, since widespread susceptibility testing is generally not routinely performed.”

As alternative treatments, Dr. Clancy pointed to the recent IDSA update, which included a stronger endorsement of fidaxomicin.

“Of course, there is also the need to assure that data on resistance to agents like fidaxomicin are generated going forward,” he noted.

The study was supported by was supported by National Institutes of Health, the National Institute of Allergy and Infectious Diseases, the Texas Medical Center Digestive Diseases Center, and the University of Texas Health Science Center. Dr. Darkoh has disclosed no relevant financial relationships. One coauthor received grant support from Merck, Entasis Pharmaceuticals, and MeMed Diagnostics. Dr. Clancy disclosed advisory board, consulting and/or research relationships with Merck, Qpex Biopharma, Shionogi, Astellas, Cidara, Scynexis, and Needham & Associates.

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

Samples from patients in the United States and Kenya show an increasing emergence of previously undetected vancomycin-resistant strains of Clostridioides difficile, sparking concern as recurrences in the treatment of C. difficile infection (CDI) continue to rise.

“Our results may help explain a decreasing effectiveness of antibiotic-based therapy in C. difficile infection, since a significant proportion of patients harboring strains with reduced susceptibility to vancomycin may not respond to treatment,” reported the authors in research published recently in Clinical Infectious Diseases.

The spread of the resistant strains “has serious public health implications, underscoring an urgent need for a comprehensive analysis of the circulating strains to help inform clinical decisions,” they added.

Commenting on the findings, Cornelius J. Clancy, MD, professor of medicine at the University of Pittsburgh, and chief of infectious diseases at the Veterans Affairs Pittsburgh Healthcare System, echoed the concern.

“The casual belief has been that [C. difficile] strains at most centers can be assumed to be vancomycin susceptible,” he told this news organization. “This study shows that this assumption can no longer be taken as a given.”

Dr. Clancy, who was not involved with this research, noted that “based on this study, there might be need for the Infectious Diseases Society of America and other organizations to offer guidance on generating good, quality surveillance data for C. difficile resistance.”

With C. difficile showing the ability to resist multiple antibiotics, drugs in the armamentarium to treat the infection have declined in recent years, and recurrences with the infection are reported in up to 25% of cases.

Oral vancomycin is recommended as the antibiotic of choice by the IDSA and the Society for Healthcare Epidemiology of America for severe as well as nonsevere cases of CDI, and although there are reports of nine vancomycin-resistant gene clusters, most involve Enterococcus.

To take a closer look at the prevalence of vancomycin-resistant C. difficile strains, first author Charles Darkoh, PhD, with the Center for Infectious Diseases at the University of Texas Health Science Center, Houston, and colleagues analyzed stool samples from patients with CDI, including 438 patients in Houston, taken between 2012 and 2017, and 98 in Nairobi, Kenya, taken in 2017.

They found that, among samples from patients in Houston, over the time period, 26% showed vancomycin nonsusceptible C. difficile isolates and 29% had isolates that were metronidazole resistant.

And among samples from the Nairobi patients, 67% harbored vancomycin-resistant isolates and 85% had isolates resistant to metronidazole.

Of note, the proportion of samples containing vancomycin-resistant C. difficile in the Houston patients showed a marked increase over time, from «complete absence» in 2012 to approximately 35% in 2017, the authors reported.

“These nonsusceptibility rates significantly exceeded prior reports from other studies conducted in the United States and Europe from 2011 to 2014, suggesting a lower percentage of resistance to both metronidazole and vancomycin,” the authors wrote.

Further experiments on mouse models infected with one of the vancomycin-resistant isolates showed that treatment with vancomycin failed to eradicate the infection, and 5-day survival was significantly lower after vancomycin treatment in those mice (25%) versus those infected with strains known to be vancomycin sensitive (50%).
 

Unrecognized genetic strains

Whole-genome sequencing of 10 of the resistant isolates showed no matches with gene clusters that have been previously recognized as being vancomycin resistant, suggesting the emergence of new clusters.

“Together, these results suggest unknown genetic elements associated with vancomycin nonsusceptibility in isolates circulating in the patient population,” the authors wrote.

Dr. Darkoh told this news organization that the research team is currently working to further investigate the patterns and mechanisms.

“We are currently working on a follow-up study for the next 5 years to find out how widespread this is,” he said. “We want to make sure it’s not necessarily just occurring in the settings we studied, and we also need to establish the mechanism of resistance.”

Further commenting on the results, Dr. Clancy noted that “the extent of resistance caught many in the field a bit off guard, as they are higher than previously reported.”

“The data are also concerning because most centers do not routinely test C. difficile for drug susceptibility.”

Dr. Clancy noted that “another immediately pressing need is to understand mechanisms of resistance. It was quite striking that vancomycin-resistant strains in this study did not carry vanA genes, pointing to previously unrecognized mechanisms of resistance.”

“As is often the case, antibiotic overuse was likely a factor in the resistances, with overtesting often leading to overtreatment of C. difficile,” Dr. Clancy said. “The situation may have been compounded by failure to appreciate how entrenched C. difficile resistance may be at certain hospitals, since widespread susceptibility testing is generally not routinely performed.”

As alternative treatments, Dr. Clancy pointed to the recent IDSA update, which included a stronger endorsement of fidaxomicin.

“Of course, there is also the need to assure that data on resistance to agents like fidaxomicin are generated going forward,” he noted.

The study was supported by was supported by National Institutes of Health, the National Institute of Allergy and Infectious Diseases, the Texas Medical Center Digestive Diseases Center, and the University of Texas Health Science Center. Dr. Darkoh has disclosed no relevant financial relationships. One coauthor received grant support from Merck, Entasis Pharmaceuticals, and MeMed Diagnostics. Dr. Clancy disclosed advisory board, consulting and/or research relationships with Merck, Qpex Biopharma, Shionogi, Astellas, Cidara, Scynexis, and Needham & Associates.

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

Samples from patients in the United States and Kenya show an increasing emergence of previously undetected vancomycin-resistant strains of Clostridioides difficile, sparking concern as recurrences in the treatment of C. difficile infection (CDI) continue to rise.

“Our results may help explain a decreasing effectiveness of antibiotic-based therapy in C. difficile infection, since a significant proportion of patients harboring strains with reduced susceptibility to vancomycin may not respond to treatment,” reported the authors in research published recently in Clinical Infectious Diseases.

The spread of the resistant strains “has serious public health implications, underscoring an urgent need for a comprehensive analysis of the circulating strains to help inform clinical decisions,” they added.

Commenting on the findings, Cornelius J. Clancy, MD, professor of medicine at the University of Pittsburgh, and chief of infectious diseases at the Veterans Affairs Pittsburgh Healthcare System, echoed the concern.

“The casual belief has been that [C. difficile] strains at most centers can be assumed to be vancomycin susceptible,” he told this news organization. “This study shows that this assumption can no longer be taken as a given.”

Dr. Clancy, who was not involved with this research, noted that “based on this study, there might be need for the Infectious Diseases Society of America and other organizations to offer guidance on generating good, quality surveillance data for C. difficile resistance.”

With C. difficile showing the ability to resist multiple antibiotics, drugs in the armamentarium to treat the infection have declined in recent years, and recurrences with the infection are reported in up to 25% of cases.

Oral vancomycin is recommended as the antibiotic of choice by the IDSA and the Society for Healthcare Epidemiology of America for severe as well as nonsevere cases of CDI, and although there are reports of nine vancomycin-resistant gene clusters, most involve Enterococcus.

To take a closer look at the prevalence of vancomycin-resistant C. difficile strains, first author Charles Darkoh, PhD, with the Center for Infectious Diseases at the University of Texas Health Science Center, Houston, and colleagues analyzed stool samples from patients with CDI, including 438 patients in Houston, taken between 2012 and 2017, and 98 in Nairobi, Kenya, taken in 2017.

They found that, among samples from patients in Houston, over the time period, 26% showed vancomycin nonsusceptible C. difficile isolates and 29% had isolates that were metronidazole resistant.

And among samples from the Nairobi patients, 67% harbored vancomycin-resistant isolates and 85% had isolates resistant to metronidazole.

Of note, the proportion of samples containing vancomycin-resistant C. difficile in the Houston patients showed a marked increase over time, from «complete absence» in 2012 to approximately 35% in 2017, the authors reported.

“These nonsusceptibility rates significantly exceeded prior reports from other studies conducted in the United States and Europe from 2011 to 2014, suggesting a lower percentage of resistance to both metronidazole and vancomycin,” the authors wrote.

Further experiments on mouse models infected with one of the vancomycin-resistant isolates showed that treatment with vancomycin failed to eradicate the infection, and 5-day survival was significantly lower after vancomycin treatment in those mice (25%) versus those infected with strains known to be vancomycin sensitive (50%).
 

Unrecognized genetic strains

Whole-genome sequencing of 10 of the resistant isolates showed no matches with gene clusters that have been previously recognized as being vancomycin resistant, suggesting the emergence of new clusters.

“Together, these results suggest unknown genetic elements associated with vancomycin nonsusceptibility in isolates circulating in the patient population,” the authors wrote.

Dr. Darkoh told this news organization that the research team is currently working to further investigate the patterns and mechanisms.

“We are currently working on a follow-up study for the next 5 years to find out how widespread this is,” he said. “We want to make sure it’s not necessarily just occurring in the settings we studied, and we also need to establish the mechanism of resistance.”

Further commenting on the results, Dr. Clancy noted that “the extent of resistance caught many in the field a bit off guard, as they are higher than previously reported.”

“The data are also concerning because most centers do not routinely test C. difficile for drug susceptibility.”

Dr. Clancy noted that “another immediately pressing need is to understand mechanisms of resistance. It was quite striking that vancomycin-resistant strains in this study did not carry vanA genes, pointing to previously unrecognized mechanisms of resistance.”

“As is often the case, antibiotic overuse was likely a factor in the resistances, with overtesting often leading to overtreatment of C. difficile,” Dr. Clancy said. “The situation may have been compounded by failure to appreciate how entrenched C. difficile resistance may be at certain hospitals, since widespread susceptibility testing is generally not routinely performed.”

As alternative treatments, Dr. Clancy pointed to the recent IDSA update, which included a stronger endorsement of fidaxomicin.

“Of course, there is also the need to assure that data on resistance to agents like fidaxomicin are generated going forward,” he noted.

The study was supported by was supported by National Institutes of Health, the National Institute of Allergy and Infectious Diseases, the Texas Medical Center Digestive Diseases Center, and the University of Texas Health Science Center. Dr. Darkoh has disclosed no relevant financial relationships. One coauthor received grant support from Merck, Entasis Pharmaceuticals, and MeMed Diagnostics. Dr. Clancy disclosed advisory board, consulting and/or research relationships with Merck, Qpex Biopharma, Shionogi, Astellas, Cidara, Scynexis, and Needham & Associates.

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

Bronchiolitis is the leading cause of infant hospitalizations in the United States and Europe, and almost one-third of these patients go on to develop asthma later in childhood.

But a multinational team of researchers has presented evidence that could avoid that outcome. They identified four different subtypes of bronchiolitis along with a decision tree that can determine which infants are most likely to develop asthma as they get older.

Reporting in the journal eClinical Medicine, Michimasa Fujiogi, MD, of Massachusetts General Hospital and Harvard University, Boston, and colleagues analyzed three multicenter prospective cohort studies that included a combined 3,081 infants hospitalized with severe bronchiolitis.

“This study added a base for the early identification of high-risk patients during early infancy,” Dr. Fujiogi said in an interview. “Using the prediction rule of this study, it is possible to identify groups at high risk of asthma during a critical period of airway development – early infancy.”

The researchers identified four clinically distinct and reproducible profiles of infants hospitalized for bronchiolitis:

• A: characterized by a history of breathing problems and eczema, rhinovirus infection, and low prevalence of respiratory syncytial virus (RSV) infection.
• B: characterized by the classic symptoms of wheezing and cough at presentation, a low prevalence of previous breathing problems and rhinovirus infection, and a high likelihood of RSV infection.
• C: the most severe group, characterized by inadequate oral intake, severe retraction at presentation, and longer hospital stays.
• D: the least ill group, with little history of breathing problems but inadequate oral intake with no or mild retraction.

Infants with profile A had the highest risk for developing asthma – more than 250% greater than with typical bronchiolitis. They were also older and were more likely to have parents who had asthma – and none had solo-RSV infection. In the overall analysis, the risk for developing asthma by age 6 or 7 was 23%.

The researchers stated that the decision tree accurately predicts the high-risk profile with high degrees of sensitivity and specificity. The decision tree used four predictors that together defined infants with profile A: RSV infection status, previous breathing problems, eczema, and parental asthma.

“Our data would facilitate the development of profile-specific prevention strategies for asthma – for example, modification of host response, prophylaxis for severe viral infection – by identifying asthma risk groups early in infancy,” Dr. Fujiogi said.

The study received funding from the National Institutes of Health. Dr. Fujiogi and coauthors have disclosed no relevant financial relationships.

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

Bronchiolitis is the leading cause of infant hospitalizations in the United States and Europe, and almost one-third of these patients go on to develop asthma later in childhood.

But a multinational team of researchers has presented evidence that could avoid that outcome. They identified four different subtypes of bronchiolitis along with a decision tree that can determine which infants are most likely to develop asthma as they get older.

Reporting in the journal eClinical Medicine, Michimasa Fujiogi, MD, of Massachusetts General Hospital and Harvard University, Boston, and colleagues analyzed three multicenter prospective cohort studies that included a combined 3,081 infants hospitalized with severe bronchiolitis.

“This study added a base for the early identification of high-risk patients during early infancy,” Dr. Fujiogi said in an interview. “Using the prediction rule of this study, it is possible to identify groups at high risk of asthma during a critical period of airway development – early infancy.”

The researchers identified four clinically distinct and reproducible profiles of infants hospitalized for bronchiolitis:

• A: characterized by a history of breathing problems and eczema, rhinovirus infection, and low prevalence of respiratory syncytial virus (RSV) infection.
• B: characterized by the classic symptoms of wheezing and cough at presentation, a low prevalence of previous breathing problems and rhinovirus infection, and a high likelihood of RSV infection.
• C: the most severe group, characterized by inadequate oral intake, severe retraction at presentation, and longer hospital stays.
• D: the least ill group, with little history of breathing problems but inadequate oral intake with no or mild retraction.

Infants with profile A had the highest risk for developing asthma – more than 250% greater than with typical bronchiolitis. They were also older and were more likely to have parents who had asthma – and none had solo-RSV infection. In the overall analysis, the risk for developing asthma by age 6 or 7 was 23%.

The researchers stated that the decision tree accurately predicts the high-risk profile with high degrees of sensitivity and specificity. The decision tree used four predictors that together defined infants with profile A: RSV infection status, previous breathing problems, eczema, and parental asthma.

“Our data would facilitate the development of profile-specific prevention strategies for asthma – for example, modification of host response, prophylaxis for severe viral infection – by identifying asthma risk groups early in infancy,” Dr. Fujiogi said.

The study received funding from the National Institutes of Health. Dr. Fujiogi and coauthors have disclosed no relevant financial relationships.

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

Bronchiolitis is the leading cause of infant hospitalizations in the United States and Europe, and almost one-third of these patients go on to develop asthma later in childhood.

But a multinational team of researchers has presented evidence that could avoid that outcome. They identified four different subtypes of bronchiolitis along with a decision tree that can determine which infants are most likely to develop asthma as they get older.

Reporting in the journal eClinical Medicine, Michimasa Fujiogi, MD, of Massachusetts General Hospital and Harvard University, Boston, and colleagues analyzed three multicenter prospective cohort studies that included a combined 3,081 infants hospitalized with severe bronchiolitis.

“This study added a base for the early identification of high-risk patients during early infancy,” Dr. Fujiogi said in an interview. “Using the prediction rule of this study, it is possible to identify groups at high risk of asthma during a critical period of airway development – early infancy.”

The researchers identified four clinically distinct and reproducible profiles of infants hospitalized for bronchiolitis:

• A: characterized by a history of breathing problems and eczema, rhinovirus infection, and low prevalence of respiratory syncytial virus (RSV) infection.
• B: characterized by the classic symptoms of wheezing and cough at presentation, a low prevalence of previous breathing problems and rhinovirus infection, and a high likelihood of RSV infection.
• C: the most severe group, characterized by inadequate oral intake, severe retraction at presentation, and longer hospital stays.
• D: the least ill group, with little history of breathing problems but inadequate oral intake with no or mild retraction.

Infants with profile A had the highest risk for developing asthma – more than 250% greater than with typical bronchiolitis. They were also older and were more likely to have parents who had asthma – and none had solo-RSV infection. In the overall analysis, the risk for developing asthma by age 6 or 7 was 23%.

The researchers stated that the decision tree accurately predicts the high-risk profile with high degrees of sensitivity and specificity. The decision tree used four predictors that together defined infants with profile A: RSV infection status, previous breathing problems, eczema, and parental asthma.

“Our data would facilitate the development of profile-specific prevention strategies for asthma – for example, modification of host response, prophylaxis for severe viral infection – by identifying asthma risk groups early in infancy,” Dr. Fujiogi said.

The study received funding from the National Institutes of Health. Dr. Fujiogi and coauthors have disclosed no relevant financial relationships.

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

Vaginal cleansing showed no reduction in morbidity when performed before unscheduled cesarean deliveries, researchers reported at the 2022 Pregnancy Meeting of the Society for Maternal-Fetal Medicine.

Several studies have evaluated vaginal cleansing prior to cesarean delivery, with mixed results. The American College of Obstetricians and Gynecologists recommends clinicians consider cleansing prior to unscheduled cesareans, but that advice appears not to be widely heeded.

The new findings, from what the researchers called the single largest study of vaginal cleansing prior to cesarean delivery in the United States, showed no difference in post-cesarean infections when the vagina was cleansed with povidone-iodine prior to unscheduled cesarean delivery.

“These findings do not support routine vaginal cleansing prior to unscheduled cesarean deliveries,” lead author Lorene Atkins Temming, MD, medical director of labor and delivery at Atrium Health Wake Forest School of Medicine, Charlotte, North Carolina, told this news organization. The research was conducted at and sponsored by Washington University School of Medicine, St. Louis, where Dr. Temming did her fellowship.

Dr. Temming’s group compared vaginal cleansing with povidone-iodine in addition to routine abdominal cleansing to abdominal cleansing alone. Among the primary outcomes of the study was the effect of cleansing on post-cesarean infectious morbidity.

“There is a higher risk of infectious complications after cesarean delivery than other gynecologic surgeries,” Dr. Temming told this news organization. “While the reason for this isn’t entirely clear, it is thought to be because cesareans are often performed after a patient’s cervix is dilated. This dilation can allow normal bacteria that live in the vagina to ascend into the uterus and can increase the risk of infections.”

Patients undergoing cesarean delivery after labor were randomly assigned to undergo preoperative abdominal cleansing only (n = 304) or preoperative abdominal cleansing plus vaginal cleansing with povidone-iodine (n = 304). Women were included in the analysis if they underwent cesareans after regular contractions and any cervical dilation, if their membranes ruptured, or if they had the procedure performed when they were more than 4 cm dilated.

The primary outcome was composite infectious morbidity, a catchall that included surgical-site infection, maternal fever, endometritis, and wound complications within 30 days after cesarean delivery. The secondary outcomes were hospital readmission, visits to the emergency department, and treatment for neonatal sepsis.

The researchers observed no significant difference in the primary composite outcome between the two groups (11.7% vs. 11.7%, P = .98; 95% confidence interval, 0.6-1.5). “Vaginal cleansing appears to be unnecessary when preoperative antibiotics and skin antisepsis are performed,” Dr. Temming said.

Jennifer L. Lew, MD, an ob/gyn at Northwestern Medicine Kishwaukee Hospital in Dekalb, Illinois, said current practice regarding preparation for unscheduled cesarean surgery includes chlorhexidine on the abdomen and povidone-iodine for introducing a Foley catheter into the urethra.

“Many patients may already have a catheter in place due to labor and epidural, so they would not need” vaginal prep, Dr. Lew said. “Currently, the standard does not require doing a vaginal prep for any cesarean sections, those in labor or not.”

The researchers have disclosed no relevant financial relationships.

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

Vaginal cleansing showed no reduction in morbidity when performed before unscheduled cesarean deliveries, researchers reported at the 2022 Pregnancy Meeting of the Society for Maternal-Fetal Medicine.

Several studies have evaluated vaginal cleansing prior to cesarean delivery, with mixed results. The American College of Obstetricians and Gynecologists recommends clinicians consider cleansing prior to unscheduled cesareans, but that advice appears not to be widely heeded.

The new findings, from what the researchers called the single largest study of vaginal cleansing prior to cesarean delivery in the United States, showed no difference in post-cesarean infections when the vagina was cleansed with povidone-iodine prior to unscheduled cesarean delivery.

“These findings do not support routine vaginal cleansing prior to unscheduled cesarean deliveries,” lead author Lorene Atkins Temming, MD, medical director of labor and delivery at Atrium Health Wake Forest School of Medicine, Charlotte, North Carolina, told this news organization. The research was conducted at and sponsored by Washington University School of Medicine, St. Louis, where Dr. Temming did her fellowship.

Dr. Temming’s group compared vaginal cleansing with povidone-iodine in addition to routine abdominal cleansing to abdominal cleansing alone. Among the primary outcomes of the study was the effect of cleansing on post-cesarean infectious morbidity.

“There is a higher risk of infectious complications after cesarean delivery than other gynecologic surgeries,” Dr. Temming told this news organization. “While the reason for this isn’t entirely clear, it is thought to be because cesareans are often performed after a patient’s cervix is dilated. This dilation can allow normal bacteria that live in the vagina to ascend into the uterus and can increase the risk of infections.”

Patients undergoing cesarean delivery after labor were randomly assigned to undergo preoperative abdominal cleansing only (n = 304) or preoperative abdominal cleansing plus vaginal cleansing with povidone-iodine (n = 304). Women were included in the analysis if they underwent cesareans after regular contractions and any cervical dilation, if their membranes ruptured, or if they had the procedure performed when they were more than 4 cm dilated.

The primary outcome was composite infectious morbidity, a catchall that included surgical-site infection, maternal fever, endometritis, and wound complications within 30 days after cesarean delivery. The secondary outcomes were hospital readmission, visits to the emergency department, and treatment for neonatal sepsis.

The researchers observed no significant difference in the primary composite outcome between the two groups (11.7% vs. 11.7%, P = .98; 95% confidence interval, 0.6-1.5). “Vaginal cleansing appears to be unnecessary when preoperative antibiotics and skin antisepsis are performed,” Dr. Temming said.

Jennifer L. Lew, MD, an ob/gyn at Northwestern Medicine Kishwaukee Hospital in Dekalb, Illinois, said current practice regarding preparation for unscheduled cesarean surgery includes chlorhexidine on the abdomen and povidone-iodine for introducing a Foley catheter into the urethra.

“Many patients may already have a catheter in place due to labor and epidural, so they would not need” vaginal prep, Dr. Lew said. “Currently, the standard does not require doing a vaginal prep for any cesarean sections, those in labor or not.”

The researchers have disclosed no relevant financial relationships.

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

Vaginal cleansing showed no reduction in morbidity when performed before unscheduled cesarean deliveries, researchers reported at the 2022 Pregnancy Meeting of the Society for Maternal-Fetal Medicine.

Several studies have evaluated vaginal cleansing prior to cesarean delivery, with mixed results. The American College of Obstetricians and Gynecologists recommends clinicians consider cleansing prior to unscheduled cesareans, but that advice appears not to be widely heeded.

The new findings, from what the researchers called the single largest study of vaginal cleansing prior to cesarean delivery in the United States, showed no difference in post-cesarean infections when the vagina was cleansed with povidone-iodine prior to unscheduled cesarean delivery.

“These findings do not support routine vaginal cleansing prior to unscheduled cesarean deliveries,” lead author Lorene Atkins Temming, MD, medical director of labor and delivery at Atrium Health Wake Forest School of Medicine, Charlotte, North Carolina, told this news organization. The research was conducted at and sponsored by Washington University School of Medicine, St. Louis, where Dr. Temming did her fellowship.

Dr. Temming’s group compared vaginal cleansing with povidone-iodine in addition to routine abdominal cleansing to abdominal cleansing alone. Among the primary outcomes of the study was the effect of cleansing on post-cesarean infectious morbidity.

“There is a higher risk of infectious complications after cesarean delivery than other gynecologic surgeries,” Dr. Temming told this news organization. “While the reason for this isn’t entirely clear, it is thought to be because cesareans are often performed after a patient’s cervix is dilated. This dilation can allow normal bacteria that live in the vagina to ascend into the uterus and can increase the risk of infections.”

Patients undergoing cesarean delivery after labor were randomly assigned to undergo preoperative abdominal cleansing only (n = 304) or preoperative abdominal cleansing plus vaginal cleansing with povidone-iodine (n = 304). Women were included in the analysis if they underwent cesareans after regular contractions and any cervical dilation, if their membranes ruptured, or if they had the procedure performed when they were more than 4 cm dilated.

The primary outcome was composite infectious morbidity, a catchall that included surgical-site infection, maternal fever, endometritis, and wound complications within 30 days after cesarean delivery. The secondary outcomes were hospital readmission, visits to the emergency department, and treatment for neonatal sepsis.

The researchers observed no significant difference in the primary composite outcome between the two groups (11.7% vs. 11.7%, P = .98; 95% confidence interval, 0.6-1.5). “Vaginal cleansing appears to be unnecessary when preoperative antibiotics and skin antisepsis are performed,” Dr. Temming said.

Jennifer L. Lew, MD, an ob/gyn at Northwestern Medicine Kishwaukee Hospital in Dekalb, Illinois, said current practice regarding preparation for unscheduled cesarean surgery includes chlorhexidine on the abdomen and povidone-iodine for introducing a Foley catheter into the urethra.

“Many patients may already have a catheter in place due to labor and epidural, so they would not need” vaginal prep, Dr. Lew said. “Currently, the standard does not require doing a vaginal prep for any cesarean sections, those in labor or not.”

The researchers have disclosed no relevant financial relationships.

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

It seems obvious that increased use of mosquito bed nets in sub-Saharan Africa would decrease the incidence of malaria, but a lingering question remained: Would controlling malaria in children under 5 years of age shift deaths to older children by delaying functional immunity?  A new report in the New England Journal of Medicine seems to have laid that concern to rest.

Malaria from Plasmodium falciparum infection exacts a significant toll in sub-Saharan Africa. According to the World Health Organization, there were about 228 million cases and 602,000 deaths from malaria in 2020 alone. About 80% of those deaths were in children less than 5 years old. In some areas, as many as 5% of children die from malaria by age 5.

Efforts to reduce the burden of malaria have been ongoing for decades. In the 1990s, insecticide-treated nets were shown to reduce illness and deaths from malaria in children.

As a result, the use of bed nets has grown significantly. In 2000, only 5% of households in sub-Saharan Africa had a net in the house. By 2020, that number had risen to 65%. From 2004 to 2019 about 1.9 billion nets were distributed in this region. The nets are estimated to have prevented more than 663 million malaria cases between 2000 and 2015.

As described in the NEJM report, public health researchers conducted a 22-year prospective longitudinal cohort study in rural southern Tanzania following 6,706 children born between 1998 and 2000. Initially, home visits were made every 4 months from May 1998 to April 2003. Remarkably, in 2019, they were able to verify the status of fully 89% of those people by reaching out to families and community/village leaders.

Günther Fink, PhD, associate professor of epidemiology and household economics, University of Basel (Switzerland), explained the approach and primary findings to this news organization. The analysis looked at three main groups – children whose parents said they always slept under treated nets, those who slept protected most of the time, and those who spent less than half the time under bed nets. The hazard ratio for death was 0.57 (95% confidence interval, 0.45-0.72) for the first two groups, compared with the least protected. The corresponding hazard ratio between age 5 and adulthood was 0.93 (95% CI, 0.58-1.49).

The findings confirmed what they had suspected. Dr. Fink summarized simply, “If you always slept under a net, you did much better than if you never slept under the net. If you slept [under a net] more than half of the time, it was much better than if you slept [under a net] less than half the time.” So the more time children slept under bed nets, the less likely they were to acquire malaria. Dr. Fink stressed that the findings showing protective efficacy persisted into adulthood. “It seems just having a healthier early life actually makes you more resilient against other future infections.”

One of the theoretical concerns was that using nets would delay developing functional immunity and that there might be an increase in mortality seen later. This study showed that did not happen.

An accompanying commentary noted that there was some potential that families receiving nets were better off than those that didn’t but concluded that such confounding had been accounted for in other analyses.

Mark Wilson, ScD, professor emeritus of epidemiology, University of Michigan, Ann Arbor, concurred. He told this news organization that the study was “very well designed,” and the researchers “did a fantastic job” in tracking patients 20 years later.

“This is astounding!” he added. “It’s very rare to find this amount of follow-up.”

Dr. Fink’s conclusion? “Bed nets protect you in the short run, and being protected in the short run is also beneficial in the long run. There is no evidence that protecting kids in early childhood is weakening them in any way. So we should keep doing this.”

Dr. Fink and Dr. Wilson report no relevant financial relationships.

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

It seems obvious that increased use of mosquito bed nets in sub-Saharan Africa would decrease the incidence of malaria, but a lingering question remained: Would controlling malaria in children under 5 years of age shift deaths to older children by delaying functional immunity?  A new report in the New England Journal of Medicine seems to have laid that concern to rest.

Malaria from Plasmodium falciparum infection exacts a significant toll in sub-Saharan Africa. According to the World Health Organization, there were about 228 million cases and 602,000 deaths from malaria in 2020 alone. About 80% of those deaths were in children less than 5 years old. In some areas, as many as 5% of children die from malaria by age 5.

Efforts to reduce the burden of malaria have been ongoing for decades. In the 1990s, insecticide-treated nets were shown to reduce illness and deaths from malaria in children.

As a result, the use of bed nets has grown significantly. In 2000, only 5% of households in sub-Saharan Africa had a net in the house. By 2020, that number had risen to 65%. From 2004 to 2019 about 1.9 billion nets were distributed in this region. The nets are estimated to have prevented more than 663 million malaria cases between 2000 and 2015.

As described in the NEJM report, public health researchers conducted a 22-year prospective longitudinal cohort study in rural southern Tanzania following 6,706 children born between 1998 and 2000. Initially, home visits were made every 4 months from May 1998 to April 2003. Remarkably, in 2019, they were able to verify the status of fully 89% of those people by reaching out to families and community/village leaders.

Günther Fink, PhD, associate professor of epidemiology and household economics, University of Basel (Switzerland), explained the approach and primary findings to this news organization. The analysis looked at three main groups – children whose parents said they always slept under treated nets, those who slept protected most of the time, and those who spent less than half the time under bed nets. The hazard ratio for death was 0.57 (95% confidence interval, 0.45-0.72) for the first two groups, compared with the least protected. The corresponding hazard ratio between age 5 and adulthood was 0.93 (95% CI, 0.58-1.49).

The findings confirmed what they had suspected. Dr. Fink summarized simply, “If you always slept under a net, you did much better than if you never slept under the net. If you slept [under a net] more than half of the time, it was much better than if you slept [under a net] less than half the time.” So the more time children slept under bed nets, the less likely they were to acquire malaria. Dr. Fink stressed that the findings showing protective efficacy persisted into adulthood. “It seems just having a healthier early life actually makes you more resilient against other future infections.”

One of the theoretical concerns was that using nets would delay developing functional immunity and that there might be an increase in mortality seen later. This study showed that did not happen.

An accompanying commentary noted that there was some potential that families receiving nets were better off than those that didn’t but concluded that such confounding had been accounted for in other analyses.

Mark Wilson, ScD, professor emeritus of epidemiology, University of Michigan, Ann Arbor, concurred. He told this news organization that the study was “very well designed,” and the researchers “did a fantastic job” in tracking patients 20 years later.

“This is astounding!” he added. “It’s very rare to find this amount of follow-up.”

Dr. Fink’s conclusion? “Bed nets protect you in the short run, and being protected in the short run is also beneficial in the long run. There is no evidence that protecting kids in early childhood is weakening them in any way. So we should keep doing this.”

Dr. Fink and Dr. Wilson report no relevant financial relationships.

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

It seems obvious that increased use of mosquito bed nets in sub-Saharan Africa would decrease the incidence of malaria, but a lingering question remained: Would controlling malaria in children under 5 years of age shift deaths to older children by delaying functional immunity?  A new report in the New England Journal of Medicine seems to have laid that concern to rest.

Malaria from Plasmodium falciparum infection exacts a significant toll in sub-Saharan Africa. According to the World Health Organization, there were about 228 million cases and 602,000 deaths from malaria in 2020 alone. About 80% of those deaths were in children less than 5 years old. In some areas, as many as 5% of children die from malaria by age 5.

Efforts to reduce the burden of malaria have been ongoing for decades. In the 1990s, insecticide-treated nets were shown to reduce illness and deaths from malaria in children.

As a result, the use of bed nets has grown significantly. In 2000, only 5% of households in sub-Saharan Africa had a net in the house. By 2020, that number had risen to 65%. From 2004 to 2019 about 1.9 billion nets were distributed in this region. The nets are estimated to have prevented more than 663 million malaria cases between 2000 and 2015.

As described in the NEJM report, public health researchers conducted a 22-year prospective longitudinal cohort study in rural southern Tanzania following 6,706 children born between 1998 and 2000. Initially, home visits were made every 4 months from May 1998 to April 2003. Remarkably, in 2019, they were able to verify the status of fully 89% of those people by reaching out to families and community/village leaders.

Günther Fink, PhD, associate professor of epidemiology and household economics, University of Basel (Switzerland), explained the approach and primary findings to this news organization. The analysis looked at three main groups – children whose parents said they always slept under treated nets, those who slept protected most of the time, and those who spent less than half the time under bed nets. The hazard ratio for death was 0.57 (95% confidence interval, 0.45-0.72) for the first two groups, compared with the least protected. The corresponding hazard ratio between age 5 and adulthood was 0.93 (95% CI, 0.58-1.49).

The findings confirmed what they had suspected. Dr. Fink summarized simply, “If you always slept under a net, you did much better than if you never slept under the net. If you slept [under a net] more than half of the time, it was much better than if you slept [under a net] less than half the time.” So the more time children slept under bed nets, the less likely they were to acquire malaria. Dr. Fink stressed that the findings showing protective efficacy persisted into adulthood. “It seems just having a healthier early life actually makes you more resilient against other future infections.”

One of the theoretical concerns was that using nets would delay developing functional immunity and that there might be an increase in mortality seen later. This study showed that did not happen.

An accompanying commentary noted that there was some potential that families receiving nets were better off than those that didn’t but concluded that such confounding had been accounted for in other analyses.

Mark Wilson, ScD, professor emeritus of epidemiology, University of Michigan, Ann Arbor, concurred. He told this news organization that the study was “very well designed,” and the researchers “did a fantastic job” in tracking patients 20 years later.

“This is astounding!” he added. “It’s very rare to find this amount of follow-up.”

Dr. Fink’s conclusion? “Bed nets protect you in the short run, and being protected in the short run is also beneficial in the long run. There is no evidence that protecting kids in early childhood is weakening them in any way. So we should keep doing this.”

Dr. Fink and Dr. Wilson report no relevant financial relationships.

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

The U.S. Food and Drug Administration has approved rilpivirine and cabotegravir (Cabenuva) to 2-month dosing for adults living with HIV-1 infection.

Cabenuva was first approved by the FDA in January 2021 to be administered once monthly to treat HIV-1 infection in virologically suppressed adults. The medication was the first injectable complete antiretroviral regimen approved by the FDA.

Cabenuva can replace a current treatment in virologically suppressed adults on a stable antiretroviral regimen with no history of treatment failure and no known or suspected resistance to rilpivirine and cabotegravir, the Janssen Pharmaceutical Companies of Johnson & Johnson said in a press release. Janssen and ViiV Healthcare codeveloped the injectable antiretroviral medication Cabenuva.

The expanded label approval “marks an important step forward in advancing the treatment landscape for people living with HIV,” said Candice Long, the president of infectious diseases and vaccines at Janssen Therapeutics, in a Feb. 1 press release. “With this milestone, adults living with HIV have a treatment option that further reduces the frequency of medication.”

This expanded approval was based on global clinical trial of 1,045 adults with HIV-1, which found Cabenuva administered every 8 weeks (3 mL dose of both cabotegravir and rilpivirine) to be noninferior to the 4-week regimen (2 mL dose of both medicines). At week 48 of the trial, the proportion of participants with viral loads above 50 copies per milliliter was 1.7% in the 2-month arm and 1.0% in the 1-month arm. The study found that rates of virological suppression were similar for both the 1-month and 2-month regimens (93.5% and 94.3%, respectively).

The most common side effects were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash. Adverse reactions reported in individuals receiving the regimen every 2 months or once monthly were similar. Cabenuva is contraindicated for patients with a hypersensitivity reaction to cabotegravir or rilpivirine or for those receiving carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, St. John’s wort, and more than one dose of systemic dexamethasone.

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

The U.S. Food and Drug Administration has approved rilpivirine and cabotegravir (Cabenuva) to 2-month dosing for adults living with HIV-1 infection.

Cabenuva was first approved by the FDA in January 2021 to be administered once monthly to treat HIV-1 infection in virologically suppressed adults. The medication was the first injectable complete antiretroviral regimen approved by the FDA.

Cabenuva can replace a current treatment in virologically suppressed adults on a stable antiretroviral regimen with no history of treatment failure and no known or suspected resistance to rilpivirine and cabotegravir, the Janssen Pharmaceutical Companies of Johnson & Johnson said in a press release. Janssen and ViiV Healthcare codeveloped the injectable antiretroviral medication Cabenuva.

The expanded label approval “marks an important step forward in advancing the treatment landscape for people living with HIV,” said Candice Long, the president of infectious diseases and vaccines at Janssen Therapeutics, in a Feb. 1 press release. “With this milestone, adults living with HIV have a treatment option that further reduces the frequency of medication.”

This expanded approval was based on global clinical trial of 1,045 adults with HIV-1, which found Cabenuva administered every 8 weeks (3 mL dose of both cabotegravir and rilpivirine) to be noninferior to the 4-week regimen (2 mL dose of both medicines). At week 48 of the trial, the proportion of participants with viral loads above 50 copies per milliliter was 1.7% in the 2-month arm and 1.0% in the 1-month arm. The study found that rates of virological suppression were similar for both the 1-month and 2-month regimens (93.5% and 94.3%, respectively).

The most common side effects were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash. Adverse reactions reported in individuals receiving the regimen every 2 months or once monthly were similar. Cabenuva is contraindicated for patients with a hypersensitivity reaction to cabotegravir or rilpivirine or for those receiving carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, St. John’s wort, and more than one dose of systemic dexamethasone.

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

The U.S. Food and Drug Administration has approved rilpivirine and cabotegravir (Cabenuva) to 2-month dosing for adults living with HIV-1 infection.

Cabenuva was first approved by the FDA in January 2021 to be administered once monthly to treat HIV-1 infection in virologically suppressed adults. The medication was the first injectable complete antiretroviral regimen approved by the FDA.

Cabenuva can replace a current treatment in virologically suppressed adults on a stable antiretroviral regimen with no history of treatment failure and no known or suspected resistance to rilpivirine and cabotegravir, the Janssen Pharmaceutical Companies of Johnson & Johnson said in a press release. Janssen and ViiV Healthcare codeveloped the injectable antiretroviral medication Cabenuva.

The expanded label approval “marks an important step forward in advancing the treatment landscape for people living with HIV,” said Candice Long, the president of infectious diseases and vaccines at Janssen Therapeutics, in a Feb. 1 press release. “With this milestone, adults living with HIV have a treatment option that further reduces the frequency of medication.”

This expanded approval was based on global clinical trial of 1,045 adults with HIV-1, which found Cabenuva administered every 8 weeks (3 mL dose of both cabotegravir and rilpivirine) to be noninferior to the 4-week regimen (2 mL dose of both medicines). At week 48 of the trial, the proportion of participants with viral loads above 50 copies per milliliter was 1.7% in the 2-month arm and 1.0% in the 1-month arm. The study found that rates of virological suppression were similar for both the 1-month and 2-month regimens (93.5% and 94.3%, respectively).

The most common side effects were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash. Adverse reactions reported in individuals receiving the regimen every 2 months or once monthly were similar. Cabenuva is contraindicated for patients with a hypersensitivity reaction to cabotegravir or rilpivirine or for those receiving carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, St. John’s wort, and more than one dose of systemic dexamethasone.

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

As rheumatologists contend with vaccine hesitancy among certain subsets of patients, the American College of Rheumatology has released updated clinical guidelines on COVID-19 vaccination for patients with rheumatic and musculoskeletal diseases (RMDs), including new recommendations on supplemental and booster doses.

The revised guidance from this fifth version of the ACR guidelines includes strongly recommending that all RMD patients receive a booster after their primary vaccine series, regardless of whether they have been naturally infected with COVID-19. In addition, they strongly recommend third supplemental doses for patients with autoimmune inflammatory rheumatic diseases (AIIRDs) who likely mounted an inadequate vaccine response, which would then be followed by a fourth booster dose as advised by the Centers for Disease Control and Prevention for immunocompromised individuals.

South_agency/Getty Images

Other recommendations include pre-exposure prophylaxis monoclonal antibody treatment for high-risk AIIRD patients, defined as those with moderate to severely compromised immune systems who may not mount an adequate immune response to COVID-19 vaccination, when it is available and authorized for emergency use by the Food and Drug Administration, as well as monoclonal antibody therapy for postexposure prophylaxis of asymptomatic, recently exposed high-risk AIIRD patients or as treatment for newly symptomatic, high-risk AIIRD patients. The ACR guidance notes that, currently, neither the monoclonal antibodies bamlanivimab and etesevimab (administered together) nor casirivimab and imdevimab (REGEN-COV), are licensed or available under an emergency use authorization given their lack of activity against the Omicron variant, the dominant strain of SARS-CoV-2 circulating in the United States.

Finally, the guidance clarified that the timing of intravenous immunoglobulin doses does not need to be modified around the administration of COVID vaccine doses, based on moderate consensus among task force members.

Vaccine hesitancy in community rheumatology practices

The revised guidelines were released just as Arthritis & Rheumatology published a new study that assessed vaccine hesitancy among rheumatology patients on immunomodulatory therapies. A three-item electronic survey was conducted at 101 offices within a community practice–based rheumatology research network and ultimately collected responses from 58,529 patients, 20,987 of whom had an AIIRD and were receiving targeted therapies like biologics or Janus kinase inhibitors.

Of the total respondents, 77% (n = 43,675) had been vaccinated, 16.9% were not vaccinated and did not plan to be, and 6.1% were not vaccinated but planned to be. However, AIIRD patients were 16% less likely to be vaccinated, compared with the other patients, such as those with osteoarthritis or osteoporosis who were not receiving disease-modifying antirheumatic drugs (76.9% vs. 87%; odds ratio, 0.84; 95% confidence interval, 0.77-0.92; P < .001). Multivariable analysis also found that older patients (OR, 1.49 per 10 years) and Asians (OR, 2.42; 95% CI, 1.77-3.33) were more likely to be vaccinated.

Courtesy UAB Photo

“Rheumatologists need to be asking their patients more than just: ‘Are you vaccinated?’ ” Jeffrey Curtis, MD, MPH, head of the ACR COVID-19 vaccine task force and a coauthor of the vaccine hesitancy study, said in an interview. “A year ago, that was a fine approach, but now they need to be asking whether you’ve been vaccinated, and with what, and how many times, and how recently. There are a whole lot of subtleties there; ‘vaccinated: yes or no’ is just the tip of the iceberg.”

His research into the vaccine hesitant includes recent anecdotal data from thousands of patients treated in local rheumatology community practices, many of whom cited long-term safety data and potential side effects as reasons why they were unwilling to get vaccinated. But despite their on-paper responses, he cautioned rheumatologists to think critically when determining which patients may truly be open to vaccination.

“If you’re designing strategies to affect vaccine hesitancy, you may be wasting your time with some people,” said Dr. Curtis, professor of medicine at the University of Alabama at Birmingham. “A critical need is to figure out who are the patients who may be amendable to more information or an intervention or a little bit more time and care, and who are the people where you know, this is a lost cause: You don’t get a flu shot, you haven’t been vaccinated for shingles, [and] you’re not going to get this one either.

“In terms of a research agenda, how do we develop efficient, simple, short screening tools?” he added. “Something with a few helpful questions, on a patient portal or an iPad, that will do a good job identifying your patients at risk who haven’t had vaccination but that you might be able to spend time with, intervene, and actually change their mind. If you spend gobs of time with everyone, you’ll help some people, but clinicians don’t have an infinite amount of time.”

One of the authors of the vaccine hesitancy study acknowledged being employed by the rheumatology research network that hosted the survey. Several others, including Dr. Curtis, reported receiving grants and consulting fees from various pharmaceutical companies.

As rheumatologists contend with vaccine hesitancy among certain subsets of patients, the American College of Rheumatology has released updated clinical guidelines on COVID-19 vaccination for patients with rheumatic and musculoskeletal diseases (RMDs), including new recommendations on supplemental and booster doses.

The revised guidance from this fifth version of the ACR guidelines includes strongly recommending that all RMD patients receive a booster after their primary vaccine series, regardless of whether they have been naturally infected with COVID-19. In addition, they strongly recommend third supplemental doses for patients with autoimmune inflammatory rheumatic diseases (AIIRDs) who likely mounted an inadequate vaccine response, which would then be followed by a fourth booster dose as advised by the Centers for Disease Control and Prevention for immunocompromised individuals.

South_agency/Getty Images

Other recommendations include pre-exposure prophylaxis monoclonal antibody treatment for high-risk AIIRD patients, defined as those with moderate to severely compromised immune systems who may not mount an adequate immune response to COVID-19 vaccination, when it is available and authorized for emergency use by the Food and Drug Administration, as well as monoclonal antibody therapy for postexposure prophylaxis of asymptomatic, recently exposed high-risk AIIRD patients or as treatment for newly symptomatic, high-risk AIIRD patients. The ACR guidance notes that, currently, neither the monoclonal antibodies bamlanivimab and etesevimab (administered together) nor casirivimab and imdevimab (REGEN-COV), are licensed or available under an emergency use authorization given their lack of activity against the Omicron variant, the dominant strain of SARS-CoV-2 circulating in the United States.

Finally, the guidance clarified that the timing of intravenous immunoglobulin doses does not need to be modified around the administration of COVID vaccine doses, based on moderate consensus among task force members.

Vaccine hesitancy in community rheumatology practices

The revised guidelines were released just as Arthritis & Rheumatology published a new study that assessed vaccine hesitancy among rheumatology patients on immunomodulatory therapies. A three-item electronic survey was conducted at 101 offices within a community practice–based rheumatology research network and ultimately collected responses from 58,529 patients, 20,987 of whom had an AIIRD and were receiving targeted therapies like biologics or Janus kinase inhibitors.

Of the total respondents, 77% (n = 43,675) had been vaccinated, 16.9% were not vaccinated and did not plan to be, and 6.1% were not vaccinated but planned to be. However, AIIRD patients were 16% less likely to be vaccinated, compared with the other patients, such as those with osteoarthritis or osteoporosis who were not receiving disease-modifying antirheumatic drugs (76.9% vs. 87%; odds ratio, 0.84; 95% confidence interval, 0.77-0.92; P < .001). Multivariable analysis also found that older patients (OR, 1.49 per 10 years) and Asians (OR, 2.42; 95% CI, 1.77-3.33) were more likely to be vaccinated.

Courtesy UAB Photo

“Rheumatologists need to be asking their patients more than just: ‘Are you vaccinated?’ ” Jeffrey Curtis, MD, MPH, head of the ACR COVID-19 vaccine task force and a coauthor of the vaccine hesitancy study, said in an interview. “A year ago, that was a fine approach, but now they need to be asking whether you’ve been vaccinated, and with what, and how many times, and how recently. There are a whole lot of subtleties there; ‘vaccinated: yes or no’ is just the tip of the iceberg.”

His research into the vaccine hesitant includes recent anecdotal data from thousands of patients treated in local rheumatology community practices, many of whom cited long-term safety data and potential side effects as reasons why they were unwilling to get vaccinated. But despite their on-paper responses, he cautioned rheumatologists to think critically when determining which patients may truly be open to vaccination.

“If you’re designing strategies to affect vaccine hesitancy, you may be wasting your time with some people,” said Dr. Curtis, professor of medicine at the University of Alabama at Birmingham. “A critical need is to figure out who are the patients who may be amendable to more information or an intervention or a little bit more time and care, and who are the people where you know, this is a lost cause: You don’t get a flu shot, you haven’t been vaccinated for shingles, [and] you’re not going to get this one either.

“In terms of a research agenda, how do we develop efficient, simple, short screening tools?” he added. “Something with a few helpful questions, on a patient portal or an iPad, that will do a good job identifying your patients at risk who haven’t had vaccination but that you might be able to spend time with, intervene, and actually change their mind. If you spend gobs of time with everyone, you’ll help some people, but clinicians don’t have an infinite amount of time.”

One of the authors of the vaccine hesitancy study acknowledged being employed by the rheumatology research network that hosted the survey. Several others, including Dr. Curtis, reported receiving grants and consulting fees from various pharmaceutical companies.

As rheumatologists contend with vaccine hesitancy among certain subsets of patients, the American College of Rheumatology has released updated clinical guidelines on COVID-19 vaccination for patients with rheumatic and musculoskeletal diseases (RMDs), including new recommendations on supplemental and booster doses.

The revised guidance from this fifth version of the ACR guidelines includes strongly recommending that all RMD patients receive a booster after their primary vaccine series, regardless of whether they have been naturally infected with COVID-19. In addition, they strongly recommend third supplemental doses for patients with autoimmune inflammatory rheumatic diseases (AIIRDs) who likely mounted an inadequate vaccine response, which would then be followed by a fourth booster dose as advised by the Centers for Disease Control and Prevention for immunocompromised individuals.

South_agency/Getty Images

Other recommendations include pre-exposure prophylaxis monoclonal antibody treatment for high-risk AIIRD patients, defined as those with moderate to severely compromised immune systems who may not mount an adequate immune response to COVID-19 vaccination, when it is available and authorized for emergency use by the Food and Drug Administration, as well as monoclonal antibody therapy for postexposure prophylaxis of asymptomatic, recently exposed high-risk AIIRD patients or as treatment for newly symptomatic, high-risk AIIRD patients. The ACR guidance notes that, currently, neither the monoclonal antibodies bamlanivimab and etesevimab (administered together) nor casirivimab and imdevimab (REGEN-COV), are licensed or available under an emergency use authorization given their lack of activity against the Omicron variant, the dominant strain of SARS-CoV-2 circulating in the United States.

Finally, the guidance clarified that the timing of intravenous immunoglobulin doses does not need to be modified around the administration of COVID vaccine doses, based on moderate consensus among task force members.

Vaccine hesitancy in community rheumatology practices

The revised guidelines were released just as Arthritis & Rheumatology published a new study that assessed vaccine hesitancy among rheumatology patients on immunomodulatory therapies. A three-item electronic survey was conducted at 101 offices within a community practice–based rheumatology research network and ultimately collected responses from 58,529 patients, 20,987 of whom had an AIIRD and were receiving targeted therapies like biologics or Janus kinase inhibitors.

Of the total respondents, 77% (n = 43,675) had been vaccinated, 16.9% were not vaccinated and did not plan to be, and 6.1% were not vaccinated but planned to be. However, AIIRD patients were 16% less likely to be vaccinated, compared with the other patients, such as those with osteoarthritis or osteoporosis who were not receiving disease-modifying antirheumatic drugs (76.9% vs. 87%; odds ratio, 0.84; 95% confidence interval, 0.77-0.92; P < .001). Multivariable analysis also found that older patients (OR, 1.49 per 10 years) and Asians (OR, 2.42; 95% CI, 1.77-3.33) were more likely to be vaccinated.

Courtesy UAB Photo

“Rheumatologists need to be asking their patients more than just: ‘Are you vaccinated?’ ” Jeffrey Curtis, MD, MPH, head of the ACR COVID-19 vaccine task force and a coauthor of the vaccine hesitancy study, said in an interview. “A year ago, that was a fine approach, but now they need to be asking whether you’ve been vaccinated, and with what, and how many times, and how recently. There are a whole lot of subtleties there; ‘vaccinated: yes or no’ is just the tip of the iceberg.”

His research into the vaccine hesitant includes recent anecdotal data from thousands of patients treated in local rheumatology community practices, many of whom cited long-term safety data and potential side effects as reasons why they were unwilling to get vaccinated. But despite their on-paper responses, he cautioned rheumatologists to think critically when determining which patients may truly be open to vaccination.

“If you’re designing strategies to affect vaccine hesitancy, you may be wasting your time with some people,” said Dr. Curtis, professor of medicine at the University of Alabama at Birmingham. “A critical need is to figure out who are the patients who may be amendable to more information or an intervention or a little bit more time and care, and who are the people where you know, this is a lost cause: You don’t get a flu shot, you haven’t been vaccinated for shingles, [and] you’re not going to get this one either.

“In terms of a research agenda, how do we develop efficient, simple, short screening tools?” he added. “Something with a few helpful questions, on a patient portal or an iPad, that will do a good job identifying your patients at risk who haven’t had vaccination but that you might be able to spend time with, intervene, and actually change their mind. If you spend gobs of time with everyone, you’ll help some people, but clinicians don’t have an infinite amount of time.”

One of the authors of the vaccine hesitancy study acknowledged being employed by the rheumatology research network that hosted the survey. Several others, including Dr. Curtis, reported receiving grants and consulting fees from various pharmaceutical companies.

It is a great mystery of infectious disease: Why are some people seemingly unaffected by illness that harms others? During the COVID-19 pandemic, we’ve seen this play out time and time again when whole families get sick except for one or two fortunate family members. And at so-called superspreader events that infect many, a lucky few typically walk away with their health intact. Did the virus never enter their bodies? Or do some people have natural resistance to pathogens they’ve never been exposed to before encoded in their genes?

Resistance to infectious disease is much more than a scientific curiosity and studying how it works can be a path to curb future outbreaks.

“In the event that we could identify what makes some people resistant, that immediately opens avenues for therapeutics that we could apply in all those other people who do suffer from the disease,” says András Spaan, MD, a microbiologist at Rockefeller University in New York.

Dr. Spaan is part of an international effort to identify genetic variations that spare people from becoming infected with SARS-CoV-2, the virus that causes COVID-19.

There’s far more research on what drives the tendency to get infectious diseases than on resistance to them. But a few researchers are investigating resistance to some of the world’s most common and deadly infectious diseases, and in a few cases, they’ve already translated these insights into treatments.

Perhaps the strongest example of how odd genes of just a few people can inspire treatments to help many comes from research on the human immunodeficiency virus (HIV), the virus that causes acquired immune deficiency syndrome (AIDS).
 

A genetic quirk

In the mid-1990s, several groups of researchers independently identified a mutation in a gene called CCR5 linked to resistance to HIV infection.

The gene encodes a protein on the surface of some white blood cells that helps set up the movement of other immune cells to fight infections. HIV, meanwhile, uses the CCR5 protein to help it enter the white blood cells that it infects.

The mutation, known as delta 32, results in a shorter than usual protein that doesn’t reach the surface of the cell. People who carry two copies of the delta 32 form of CCR5 do not have any CCR5 protein on the outside of their white blood cells.

Researchers, led by molecular immunologist Philip Murphy, MD, at the National Institute of Allergy and Infectious Diseases in Bethesda, Md, showed in 1997 that people with two copies of the mutation were unusually common among a group of men who were at especially high risk of HIV exposure, but had never contracted the virus. And out of more than 700 HIV-positive people, none carried two copies of CCR5 delta 32.

Pharmaceutical companies used these insights to develop drugs to block CCR5 and delay the development of AIDS. For instance, the drug maraviroc, marketed by Pfizer, was approved for use in HIV-positive people in 2007.

Only a few examples of this kind of inborn, genetically determined complete resistance to infection have ever been heard of. All of them involve cell-surface molecules that are believed to help a virus or other pathogen gain entry to the cell.
 

Locking out illness

“The first step for any intracellular pathogen is getting inside the cell. And if you’re missing the doorway, then the virus can’t accomplish the first step in its life cycle,” Dr. Murphy says. “Getting inside is fundamental.”

Changes in cell-surface molecules can also make someone more likely to have an infection or severe disease. One such group of cell-surface molecules that have been linked to both increasing and decreasing the risk of various infections are histo-blood group antigens. The most familiar members of this group are the molecules that define blood types A, B, and O.

Scientists have also identified one example of total resistance to infection involving these molecules. In 2003, researchers showed that people who lack a functional copy of a gene known as FUT2 cannot be infected with Norwalk virus, one of more than 30 viruses in the norovirus family that cause illness in the digestive tract.

The gene FUT2 encodes an enzyme that determines whether or not blood group antigens are found in a person’s saliva and other body fluids as well as on their red blood cells.

“It didn’t matter how many virus particles we challenged an individual with, if they did not have that first enzyme, they did not get infected,” says researcher Lisa Lindesmith, a virologist at the University of North Carolina in Chapel Hill.
 

No norovirus

Norwalk is a relatively rare type of norovirus. But FUT2 deficiency also provides some protection against the most common strains of norovirus, known as GII.4, which have periodically swept across the world over the past quarter-century. These illnesses take an especially heavy toll on children in the developing world, causing malnutrition and contributing to infant and child deaths.

But progress in translating these insights about genetic resistance into drugs or other things that could reduce the burden of noroviruses has been slow.

“The biggest barrier here is lack of ability to study the virus outside of humans,” Lindesmith says.

Noroviruses are very difficult to grow in the lab, “and there’s no small animal model of gastrointestinal illness caused by the viruses.”

We are clearly making giant strides in improving those skills,” says Lindesmith. “But we are just not quite there yet.”

In the years before COVID-19 emerged, tuberculosis was responsible for the largest number of annual worldwide deaths from an infectious disease. It’s a lung disease caused by the bacterium Mycobacterium tuberculosis, and it has been a pandemic for thousands of years.

Some 85%-95% of people with intact immune systems who are infected with TB control the infection and never get active lung disease. And some people who have intense, continuing exposure to the bacterium, which is spread through droplets and aerosols from people with active lung disease, apparently never become infected at all.
 

Thwarting uberculosis

Understanding the ways of these different forms of resistance could help in the search for vaccines, treatments, and other ways to fight tuberculosis, says Elouise Kroon, MD, a graduate student at Stellenbosch University in Cape Town, South Africa.

“What makes it particularly hard to study is the fact that there is no gold standard to measure infection,” she says. “So, what we do is infer infection from two different types of tests” -- a skin test and a blood test that measure different kinds of immune response to molecules from the bacterium.

Dr. Kroon and other researchers have studied resistance to infection by following people living in the same household as those with active lung disease or people who live and work in crowded conditions in high-risk communities. But not all such studies have used the same definition of so-called resisters, documented exposure in the same way, or followed up to ensure that people continue to test negative over the long term.

The best clue that has emerged from studies so far links resistance to infection to certain variations in immune molecules known as HLA class II antigens, says Marlo Möller, PhD, a professor in the TB Host Genetics Research Group at Stellenbosch University.

“That always seems to pop up everywhere. But the rest is not so obvious,” she says. “A lot of the studies don’t find the same thing. It’s different in different populations,” which may be a result of the long evolutionary history between tuberculosis and humans, as well as the fact that different strains of the bacterium are prevalent in different parts of the world.

COVID-19 is a much newer infectious disease, but teasing out how it contributes to both severe illness and resistance to infection is still a major task.
 

Overcoming COVID

Early in the pandemic, research by the COVID Human Genetic Effort, the international consortium that Dr. Spaan is part of, linked severe COVID-19 pneumonia to the lack of immune molecules known as type I interferons and to antibodies produced by the body that destroy these molecules. Together, these mechanisms explain about one-fifth of severe COVID-19 cases, the researchers reported in 2021.

A few studies by other groups have explored resistance to COVID-19 infection, suggesting that reduced risk of contracting the virus is tied to certain blood group factors. People with Type O blood appear to be at slightly reduced risk of infection, for example.

But the studies done so far are designed to find common genetic variations, which generally have a small effect on resistance. Now, genetic researchers are launching an effort to identify genetic resistance factors with a big effect, even if they are vanishingly rare.

The group is recruiting people who did not become infected with COVID-19 despite heavy exposure, such as those living in households where all the other members got sick or people who were exposed to a superspreader event but did not become ill. As with tuberculosis, being certain that someone has not been infected with the virus can be tricky, but the team is using several blood tests to home in on the people most likely to have escaped infection.

They plan to sequence the genomes of these people to identify things that strongly affect infection risk, then do more laboratory studies to try to tease out the means of resistance.

Their work is inspired by earlier efforts to uncover inborn resistance to infections, Dr. Spaan says. Despite the lack of known examples of such resistance, he is optimistic about the possibilities. Those earlier efforts took place in “a different epoch,” before there were rapid sequencing technologies, Dr. Spaan says.

“Now we have modern technologies to do this more systematically.”

The emergence of viral variants such as the Delta and Omicron COVID strains raises the stakes of the work, he continues.

“The need to unravel these inborn mechanisms of resistance to COVID has become even more important because of these new variants and the anticipation that we will have COVID with us for years.”

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

It is a great mystery of infectious disease: Why are some people seemingly unaffected by illness that harms others? During the COVID-19 pandemic, we’ve seen this play out time and time again when whole families get sick except for one or two fortunate family members. And at so-called superspreader events that infect many, a lucky few typically walk away with their health intact. Did the virus never enter their bodies? Or do some people have natural resistance to pathogens they’ve never been exposed to before encoded in their genes?

Resistance to infectious disease is much more than a scientific curiosity and studying how it works can be a path to curb future outbreaks.

“In the event that we could identify what makes some people resistant, that immediately opens avenues for therapeutics that we could apply in all those other people who do suffer from the disease,” says András Spaan, MD, a microbiologist at Rockefeller University in New York.

Dr. Spaan is part of an international effort to identify genetic variations that spare people from becoming infected with SARS-CoV-2, the virus that causes COVID-19.

There’s far more research on what drives the tendency to get infectious diseases than on resistance to them. But a few researchers are investigating resistance to some of the world’s most common and deadly infectious diseases, and in a few cases, they’ve already translated these insights into treatments.

Perhaps the strongest example of how odd genes of just a few people can inspire treatments to help many comes from research on the human immunodeficiency virus (HIV), the virus that causes acquired immune deficiency syndrome (AIDS).
 

A genetic quirk

In the mid-1990s, several groups of researchers independently identified a mutation in a gene called CCR5 linked to resistance to HIV infection.

The gene encodes a protein on the surface of some white blood cells that helps set up the movement of other immune cells to fight infections. HIV, meanwhile, uses the CCR5 protein to help it enter the white blood cells that it infects.

The mutation, known as delta 32, results in a shorter than usual protein that doesn’t reach the surface of the cell. People who carry two copies of the delta 32 form of CCR5 do not have any CCR5 protein on the outside of their white blood cells.

Researchers, led by molecular immunologist Philip Murphy, MD, at the National Institute of Allergy and Infectious Diseases in Bethesda, Md, showed in 1997 that people with two copies of the mutation were unusually common among a group of men who were at especially high risk of HIV exposure, but had never contracted the virus. And out of more than 700 HIV-positive people, none carried two copies of CCR5 delta 32.

Pharmaceutical companies used these insights to develop drugs to block CCR5 and delay the development of AIDS. For instance, the drug maraviroc, marketed by Pfizer, was approved for use in HIV-positive people in 2007.

Only a few examples of this kind of inborn, genetically determined complete resistance to infection have ever been heard of. All of them involve cell-surface molecules that are believed to help a virus or other pathogen gain entry to the cell.
 

Locking out illness

“The first step for any intracellular pathogen is getting inside the cell. And if you’re missing the doorway, then the virus can’t accomplish the first step in its life cycle,” Dr. Murphy says. “Getting inside is fundamental.”

Changes in cell-surface molecules can also make someone more likely to have an infection or severe disease. One such group of cell-surface molecules that have been linked to both increasing and decreasing the risk of various infections are histo-blood group antigens. The most familiar members of this group are the molecules that define blood types A, B, and O.

Scientists have also identified one example of total resistance to infection involving these molecules. In 2003, researchers showed that people who lack a functional copy of a gene known as FUT2 cannot be infected with Norwalk virus, one of more than 30 viruses in the norovirus family that cause illness in the digestive tract.

The gene FUT2 encodes an enzyme that determines whether or not blood group antigens are found in a person’s saliva and other body fluids as well as on their red blood cells.

“It didn’t matter how many virus particles we challenged an individual with, if they did not have that first enzyme, they did not get infected,” says researcher Lisa Lindesmith, a virologist at the University of North Carolina in Chapel Hill.
 

No norovirus

Norwalk is a relatively rare type of norovirus. But FUT2 deficiency also provides some protection against the most common strains of norovirus, known as GII.4, which have periodically swept across the world over the past quarter-century. These illnesses take an especially heavy toll on children in the developing world, causing malnutrition and contributing to infant and child deaths.

But progress in translating these insights about genetic resistance into drugs or other things that could reduce the burden of noroviruses has been slow.

“The biggest barrier here is lack of ability to study the virus outside of humans,” Lindesmith says.

Noroviruses are very difficult to grow in the lab, “and there’s no small animal model of gastrointestinal illness caused by the viruses.”

We are clearly making giant strides in improving those skills,” says Lindesmith. “But we are just not quite there yet.”

In the years before COVID-19 emerged, tuberculosis was responsible for the largest number of annual worldwide deaths from an infectious disease. It’s a lung disease caused by the bacterium Mycobacterium tuberculosis, and it has been a pandemic for thousands of years.

Some 85%-95% of people with intact immune systems who are infected with TB control the infection and never get active lung disease. And some people who have intense, continuing exposure to the bacterium, which is spread through droplets and aerosols from people with active lung disease, apparently never become infected at all.
 

Thwarting uberculosis

Understanding the ways of these different forms of resistance could help in the search for vaccines, treatments, and other ways to fight tuberculosis, says Elouise Kroon, MD, a graduate student at Stellenbosch University in Cape Town, South Africa.

“What makes it particularly hard to study is the fact that there is no gold standard to measure infection,” she says. “So, what we do is infer infection from two different types of tests” -- a skin test and a blood test that measure different kinds of immune response to molecules from the bacterium.

Dr. Kroon and other researchers have studied resistance to infection by following people living in the same household as those with active lung disease or people who live and work in crowded conditions in high-risk communities. But not all such studies have used the same definition of so-called resisters, documented exposure in the same way, or followed up to ensure that people continue to test negative over the long term.

The best clue that has emerged from studies so far links resistance to infection to certain variations in immune molecules known as HLA class II antigens, says Marlo Möller, PhD, a professor in the TB Host Genetics Research Group at Stellenbosch University.

“That always seems to pop up everywhere. But the rest is not so obvious,” she says. “A lot of the studies don’t find the same thing. It’s different in different populations,” which may be a result of the long evolutionary history between tuberculosis and humans, as well as the fact that different strains of the bacterium are prevalent in different parts of the world.

COVID-19 is a much newer infectious disease, but teasing out how it contributes to both severe illness and resistance to infection is still a major task.
 

Overcoming COVID

Early in the pandemic, research by the COVID Human Genetic Effort, the international consortium that Dr. Spaan is part of, linked severe COVID-19 pneumonia to the lack of immune molecules known as type I interferons and to antibodies produced by the body that destroy these molecules. Together, these mechanisms explain about one-fifth of severe COVID-19 cases, the researchers reported in 2021.

A few studies by other groups have explored resistance to COVID-19 infection, suggesting that reduced risk of contracting the virus is tied to certain blood group factors. People with Type O blood appear to be at slightly reduced risk of infection, for example.

But the studies done so far are designed to find common genetic variations, which generally have a small effect on resistance. Now, genetic researchers are launching an effort to identify genetic resistance factors with a big effect, even if they are vanishingly rare.

The group is recruiting people who did not become infected with COVID-19 despite heavy exposure, such as those living in households where all the other members got sick or people who were exposed to a superspreader event but did not become ill. As with tuberculosis, being certain that someone has not been infected with the virus can be tricky, but the team is using several blood tests to home in on the people most likely to have escaped infection.

They plan to sequence the genomes of these people to identify things that strongly affect infection risk, then do more laboratory studies to try to tease out the means of resistance.

Their work is inspired by earlier efforts to uncover inborn resistance to infections, Dr. Spaan says. Despite the lack of known examples of such resistance, he is optimistic about the possibilities. Those earlier efforts took place in “a different epoch,” before there were rapid sequencing technologies, Dr. Spaan says.

“Now we have modern technologies to do this more systematically.”

The emergence of viral variants such as the Delta and Omicron COVID strains raises the stakes of the work, he continues.

“The need to unravel these inborn mechanisms of resistance to COVID has become even more important because of these new variants and the anticipation that we will have COVID with us for years.”

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

It is a great mystery of infectious disease: Why are some people seemingly unaffected by illness that harms others? During the COVID-19 pandemic, we’ve seen this play out time and time again when whole families get sick except for one or two fortunate family members. And at so-called superspreader events that infect many, a lucky few typically walk away with their health intact. Did the virus never enter their bodies? Or do some people have natural resistance to pathogens they’ve never been exposed to before encoded in their genes?

Resistance to infectious disease is much more than a scientific curiosity and studying how it works can be a path to curb future outbreaks.

“In the event that we could identify what makes some people resistant, that immediately opens avenues for therapeutics that we could apply in all those other people who do suffer from the disease,” says András Spaan, MD, a microbiologist at Rockefeller University in New York.

Dr. Spaan is part of an international effort to identify genetic variations that spare people from becoming infected with SARS-CoV-2, the virus that causes COVID-19.

There’s far more research on what drives the tendency to get infectious diseases than on resistance to them. But a few researchers are investigating resistance to some of the world’s most common and deadly infectious diseases, and in a few cases, they’ve already translated these insights into treatments.

Perhaps the strongest example of how odd genes of just a few people can inspire treatments to help many comes from research on the human immunodeficiency virus (HIV), the virus that causes acquired immune deficiency syndrome (AIDS).
 

A genetic quirk

In the mid-1990s, several groups of researchers independently identified a mutation in a gene called CCR5 linked to resistance to HIV infection.

The gene encodes a protein on the surface of some white blood cells that helps set up the movement of other immune cells to fight infections. HIV, meanwhile, uses the CCR5 protein to help it enter the white blood cells that it infects.

The mutation, known as delta 32, results in a shorter than usual protein that doesn’t reach the surface of the cell. People who carry two copies of the delta 32 form of CCR5 do not have any CCR5 protein on the outside of their white blood cells.

Researchers, led by molecular immunologist Philip Murphy, MD, at the National Institute of Allergy and Infectious Diseases in Bethesda, Md, showed in 1997 that people with two copies of the mutation were unusually common among a group of men who were at especially high risk of HIV exposure, but had never contracted the virus. And out of more than 700 HIV-positive people, none carried two copies of CCR5 delta 32.

Pharmaceutical companies used these insights to develop drugs to block CCR5 and delay the development of AIDS. For instance, the drug maraviroc, marketed by Pfizer, was approved for use in HIV-positive people in 2007.

Only a few examples of this kind of inborn, genetically determined complete resistance to infection have ever been heard of. All of them involve cell-surface molecules that are believed to help a virus or other pathogen gain entry to the cell.
 

Locking out illness

“The first step for any intracellular pathogen is getting inside the cell. And if you’re missing the doorway, then the virus can’t accomplish the first step in its life cycle,” Dr. Murphy says. “Getting inside is fundamental.”

Changes in cell-surface molecules can also make someone more likely to have an infection or severe disease. One such group of cell-surface molecules that have been linked to both increasing and decreasing the risk of various infections are histo-blood group antigens. The most familiar members of this group are the molecules that define blood types A, B, and O.

Scientists have also identified one example of total resistance to infection involving these molecules. In 2003, researchers showed that people who lack a functional copy of a gene known as FUT2 cannot be infected with Norwalk virus, one of more than 30 viruses in the norovirus family that cause illness in the digestive tract.

The gene FUT2 encodes an enzyme that determines whether or not blood group antigens are found in a person’s saliva and other body fluids as well as on their red blood cells.

“It didn’t matter how many virus particles we challenged an individual with, if they did not have that first enzyme, they did not get infected,” says researcher Lisa Lindesmith, a virologist at the University of North Carolina in Chapel Hill.
 

No norovirus

Norwalk is a relatively rare type of norovirus. But FUT2 deficiency also provides some protection against the most common strains of norovirus, known as GII.4, which have periodically swept across the world over the past quarter-century. These illnesses take an especially heavy toll on children in the developing world, causing malnutrition and contributing to infant and child deaths.

But progress in translating these insights about genetic resistance into drugs or other things that could reduce the burden of noroviruses has been slow.

“The biggest barrier here is lack of ability to study the virus outside of humans,” Lindesmith says.

Noroviruses are very difficult to grow in the lab, “and there’s no small animal model of gastrointestinal illness caused by the viruses.”

We are clearly making giant strides in improving those skills,” says Lindesmith. “But we are just not quite there yet.”

In the years before COVID-19 emerged, tuberculosis was responsible for the largest number of annual worldwide deaths from an infectious disease. It’s a lung disease caused by the bacterium Mycobacterium tuberculosis, and it has been a pandemic for thousands of years.

Some 85%-95% of people with intact immune systems who are infected with TB control the infection and never get active lung disease. And some people who have intense, continuing exposure to the bacterium, which is spread through droplets and aerosols from people with active lung disease, apparently never become infected at all.
 

Thwarting uberculosis

Understanding the ways of these different forms of resistance could help in the search for vaccines, treatments, and other ways to fight tuberculosis, says Elouise Kroon, MD, a graduate student at Stellenbosch University in Cape Town, South Africa.

“What makes it particularly hard to study is the fact that there is no gold standard to measure infection,” she says. “So, what we do is infer infection from two different types of tests” -- a skin test and a blood test that measure different kinds of immune response to molecules from the bacterium.

Dr. Kroon and other researchers have studied resistance to infection by following people living in the same household as those with active lung disease or people who live and work in crowded conditions in high-risk communities. But not all such studies have used the same definition of so-called resisters, documented exposure in the same way, or followed up to ensure that people continue to test negative over the long term.

The best clue that has emerged from studies so far links resistance to infection to certain variations in immune molecules known as HLA class II antigens, says Marlo Möller, PhD, a professor in the TB Host Genetics Research Group at Stellenbosch University.

“That always seems to pop up everywhere. But the rest is not so obvious,” she says. “A lot of the studies don’t find the same thing. It’s different in different populations,” which may be a result of the long evolutionary history between tuberculosis and humans, as well as the fact that different strains of the bacterium are prevalent in different parts of the world.

COVID-19 is a much newer infectious disease, but teasing out how it contributes to both severe illness and resistance to infection is still a major task.
 

Overcoming COVID

Early in the pandemic, research by the COVID Human Genetic Effort, the international consortium that Dr. Spaan is part of, linked severe COVID-19 pneumonia to the lack of immune molecules known as type I interferons and to antibodies produced by the body that destroy these molecules. Together, these mechanisms explain about one-fifth of severe COVID-19 cases, the researchers reported in 2021.

A few studies by other groups have explored resistance to COVID-19 infection, suggesting that reduced risk of contracting the virus is tied to certain blood group factors. People with Type O blood appear to be at slightly reduced risk of infection, for example.

But the studies done so far are designed to find common genetic variations, which generally have a small effect on resistance. Now, genetic researchers are launching an effort to identify genetic resistance factors with a big effect, even if they are vanishingly rare.

The group is recruiting people who did not become infected with COVID-19 despite heavy exposure, such as those living in households where all the other members got sick or people who were exposed to a superspreader event but did not become ill. As with tuberculosis, being certain that someone has not been infected with the virus can be tricky, but the team is using several blood tests to home in on the people most likely to have escaped infection.

They plan to sequence the genomes of these people to identify things that strongly affect infection risk, then do more laboratory studies to try to tease out the means of resistance.

Their work is inspired by earlier efforts to uncover inborn resistance to infections, Dr. Spaan says. Despite the lack of known examples of such resistance, he is optimistic about the possibilities. Those earlier efforts took place in “a different epoch,” before there were rapid sequencing technologies, Dr. Spaan says.

“Now we have modern technologies to do this more systematically.”

The emergence of viral variants such as the Delta and Omicron COVID strains raises the stakes of the work, he continues.

“The need to unravel these inborn mechanisms of resistance to COVID has become even more important because of these new variants and the anticipation that we will have COVID with us for years.”

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

Americans who have received a COVID-19 booster shot are 97 times less likely to die from the coronavirus than those who aren’t vaccinated, according to a new update from the CDC.

In addition, fully vaccinated Americans — meaning those with up to two doses, but no booster — are 14 times less likely to die from COVID-19 than unvaccinated people.

“These data confirm that vaccination and boosting continues to protect against severe illness and hospitalization, even during the Omicron surge,” Rochelle Walensky, MD, director of the CDC, said during a briefing by the White House COVID-19 Response Team.

“If you are not up to date on your COVID-19 vaccinations, you have not optimized your protection against severe disease and death, and you should get vaccinated and boosted if you are eligible,” she said.

Dr. Walensky presented the latest numbers on Feb. 2 based on reports from 25 jurisdictions in early December. The number of average weekly deaths for those who were unvaccinated was 9.7 per 100,000 people, as compared with 0.7 of those who were vaccinated and 0.1 of those who had received a booster.

“The data are really stunningly obvious why a booster is really very important,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said during the briefing.

Dr. Fauci also encouraged vaccination for those who are pregnant and couples who may want to conceive in the near feature. He highlighted two recent studies that found vaccination in either partner didn’t affect fertility, including in vitro fertilization.

Meanwhile, fertility fell temporarily among men who were infected with the coronavirus. Couples were 18% less likely to conceive if the male partner had contracted the coronavirus within 60 days before a menstrual cycle.

“New data adds to previous studies that indicate that COVID-19 vaccination does not negatively impact fertility,” Dr. Fauci said. “Vaccination is recommended for people who are trying to get pregnant now or might become pregnant in the future, as well as their partners.”

About 80% of eligible Americans have received at least one vaccine dose, and 68% are fully vaccinated, according to the latest CDC data. About 51% of those who are eligible for a booster dose have received one.

The FDA could authorize the Pfizer vaccine for children under age 5 later this month. When that happens, about 18 million children will qualify for a shot, Jeff Zients, coordinator of the White House COVID-19 Response Team, said during the briefing. The Biden administration is already working on distribution plans for the shot for young kids, he added.

“We’ll be ready to start getting shots in arms soon after FDA and CDC make their decisions,” he said.

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

Americans who have received a COVID-19 booster shot are 97 times less likely to die from the coronavirus than those who aren’t vaccinated, according to a new update from the CDC.

In addition, fully vaccinated Americans — meaning those with up to two doses, but no booster — are 14 times less likely to die from COVID-19 than unvaccinated people.

“These data confirm that vaccination and boosting continues to protect against severe illness and hospitalization, even during the Omicron surge,” Rochelle Walensky, MD, director of the CDC, said during a briefing by the White House COVID-19 Response Team.

“If you are not up to date on your COVID-19 vaccinations, you have not optimized your protection against severe disease and death, and you should get vaccinated and boosted if you are eligible,” she said.

Dr. Walensky presented the latest numbers on Feb. 2 based on reports from 25 jurisdictions in early December. The number of average weekly deaths for those who were unvaccinated was 9.7 per 100,000 people, as compared with 0.7 of those who were vaccinated and 0.1 of those who had received a booster.

“The data are really stunningly obvious why a booster is really very important,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said during the briefing.

Dr. Fauci also encouraged vaccination for those who are pregnant and couples who may want to conceive in the near feature. He highlighted two recent studies that found vaccination in either partner didn’t affect fertility, including in vitro fertilization.

Meanwhile, fertility fell temporarily among men who were infected with the coronavirus. Couples were 18% less likely to conceive if the male partner had contracted the coronavirus within 60 days before a menstrual cycle.

“New data adds to previous studies that indicate that COVID-19 vaccination does not negatively impact fertility,” Dr. Fauci said. “Vaccination is recommended for people who are trying to get pregnant now or might become pregnant in the future, as well as their partners.”

About 80% of eligible Americans have received at least one vaccine dose, and 68% are fully vaccinated, according to the latest CDC data. About 51% of those who are eligible for a booster dose have received one.

The FDA could authorize the Pfizer vaccine for children under age 5 later this month. When that happens, about 18 million children will qualify for a shot, Jeff Zients, coordinator of the White House COVID-19 Response Team, said during the briefing. The Biden administration is already working on distribution plans for the shot for young kids, he added.

“We’ll be ready to start getting shots in arms soon after FDA and CDC make their decisions,” he said.

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

Americans who have received a COVID-19 booster shot are 97 times less likely to die from the coronavirus than those who aren’t vaccinated, according to a new update from the CDC.

In addition, fully vaccinated Americans — meaning those with up to two doses, but no booster — are 14 times less likely to die from COVID-19 than unvaccinated people.

“These data confirm that vaccination and boosting continues to protect against severe illness and hospitalization, even during the Omicron surge,” Rochelle Walensky, MD, director of the CDC, said during a briefing by the White House COVID-19 Response Team.

“If you are not up to date on your COVID-19 vaccinations, you have not optimized your protection against severe disease and death, and you should get vaccinated and boosted if you are eligible,” she said.

Dr. Walensky presented the latest numbers on Feb. 2 based on reports from 25 jurisdictions in early December. The number of average weekly deaths for those who were unvaccinated was 9.7 per 100,000 people, as compared with 0.7 of those who were vaccinated and 0.1 of those who had received a booster.

“The data are really stunningly obvious why a booster is really very important,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said during the briefing.

Dr. Fauci also encouraged vaccination for those who are pregnant and couples who may want to conceive in the near feature. He highlighted two recent studies that found vaccination in either partner didn’t affect fertility, including in vitro fertilization.

Meanwhile, fertility fell temporarily among men who were infected with the coronavirus. Couples were 18% less likely to conceive if the male partner had contracted the coronavirus within 60 days before a menstrual cycle.

“New data adds to previous studies that indicate that COVID-19 vaccination does not negatively impact fertility,” Dr. Fauci said. “Vaccination is recommended for people who are trying to get pregnant now or might become pregnant in the future, as well as their partners.”

About 80% of eligible Americans have received at least one vaccine dose, and 68% are fully vaccinated, according to the latest CDC data. About 51% of those who are eligible for a booster dose have received one.

The FDA could authorize the Pfizer vaccine for children under age 5 later this month. When that happens, about 18 million children will qualify for a shot, Jeff Zients, coordinator of the White House COVID-19 Response Team, said during the briefing. The Biden administration is already working on distribution plans for the shot for young kids, he added.

“We’ll be ready to start getting shots in arms soon after FDA and CDC make their decisions,” he said.

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