Immunology

New surveillance data from the Vaccine Adverse Event Reporting System (VAERS) back previous findings of increased risk for Guillain-Barré syndrome (GBS) after receiving the Janssen COVID-19 vaccine (Ad26.COV2.S).

Over 14 months, GBS reporting rates within 21 and 42 days of administration of Janssen’s replication-incompetent adenoviral vector vaccine were approximately 9 to 12 times higher than after administration of the Pfizer-BioNTech (BNT162b2) or the Moderna (mRNA-1273) mRNA COVID vaccines.

Additionally, observed GBS cases after the Janssen shot were 2 to 3 times greater than expected, based on background rates within 21 and 42 days of vaccination.

Conversely, and confirming prior data, there was no increased risk for GBS with the Pfizer or Moderna vaccines and no significant difference between observed and expected numbers of GBS cases after either mRNA COVID-19 vaccine.

The findings were published online  in JAMA Network Open.
 

More precise risk estimates

Winston Abara, MD, with the U.S. Centers for Disease Control and Prevention, and colleagues analyzed GBS reports submitted to the VAERS between December 2020 and January 2022. 

Among 487.6 million COVID-19 vaccine doses administered, 3.7% were Janssen’s Ad26.COV2.S vaccine, 54.7% were Pfizer’s BNT162b2 vaccine, and 41.6% were Moderna’s mRNA-1273 vaccine.

There were 295 verified reports of GBS identified after COVID-19 vaccination. Of these, 209 occurred within 21 days of vaccination and 253 within 42 days.

Within 21 days of vaccination, GBS reporting rates per 1 million doses were 3.29 for the Janssen vaccine versus 0.29 and 0.35 for the Pfizer and Moderna vaccines, respectively. Within 42 days of vaccination, reporting rates per 1 million doses were 4.07, 0.34, and 0.44, respectively.

Also within 21 days of vaccination, GBS reporting rates were significantly higher with the Janssen vaccine than the Pfizer vaccine (reporting rate ratio, 11.40) and the Moderna vaccine (RRR, 9.26). Similar findings were observed within 42 days after vaccination.

The observed-to-expected ratios were 3.79 for 21-day and 2.34 for 42-day intervals after receipt of the Janssen vaccine, and less than 1 (not significant) after the Pfizer or Moderna vaccine within both post-vaccination periods.

“Unlike prior studies, our analysis included all U.S. reports of verified GBS cases that met the Brighton Collaboration GBS case definition criteria (Brighton Levels 1, 2, and 3) submitted over a 14-month surveillance period to the to the Vaccine Adverse Event Reporting System,” Dr. Abara said in an interview. “Because we used all U.S. reports, the sample of verified GBS cases in this analysis is larger than other studies. Therefore, it may provide a more precise estimate of the GBS risk within 21 and 42 days after mRNA and Ad26.COV2.S vaccination,” he said.
 

‘Remarkably low’ use

Nicola Klein, MD, PhD, Kaiser Permanente Vaccine Study Center, Oakland, Calif., noted that this is a “nice confirmatory analysis that supports and further expands what’s been observed before.”

Last year, as reported by this news organization, Dr. Klein and colleagues reported data from the Vaccine Safety Datalink confirming a small but statistically significant increased risk for GBS in the 3 weeks after receipt of the Janssen COVID-19 vaccine but not the Pfizer or Moderna vaccines.

Unlike VAERS, the Vaccine Safety Datalink is not a reporting system. It’s an active surveillance of medical records in the Kaiser Permanente system. The VAERS is a passive system, so it requires individuals to report GBS cases to the VAERS team, Dr. Klein explained.

So although the two studies are slightly different, overall, the VAERS data is “consistent with what we found,” she said.

Also weighing in, C. Buddy Creech, MD, MPH, director of the Vanderbilt Vaccine Research Program and professor of pediatrics at the Vanderbilt University School of Medicine, Nashville, Tenn., said it is “important to realize that GBS had been observed after adenovirus-vectored vaccines earlier in the pandemic, both for the AstraZeneca vaccine and the Janssen vaccine.”

The Advisory Committee on Immunization Practices (ACIP) preferentially recommends that people age 18 years and older receive an mRNA COVID-19 vaccine rather than the Janssen adenoviral vector vaccine when both types of COVID-19 vaccine are available.

“Thus, the use of the Janssen vaccine is remarkably low in the U.S. right now,” Dr. Creech said.

“Nevertheless, we have a firm commitment, both scientifically and ethically, to track potential side effects after vaccination and to make sure that the vaccines in use for COVID, and other important infectious diseases, are safe and effective,” he added.

The study had no commercial funding. Dr. Abara and Dr. Creech have reported no relevant financial relationships. Dr. Klein reported having received grants from Pfizer research support for a COVID vaccine clinical trial, as well as grants from Merck, GlaxoSmithKline, Sanofi Pasteur, and Protein Science (now Sanofi Pasteur).

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

New surveillance data from the Vaccine Adverse Event Reporting System (VAERS) back previous findings of increased risk for Guillain-Barré syndrome (GBS) after receiving the Janssen COVID-19 vaccine (Ad26.COV2.S).

Over 14 months, GBS reporting rates within 21 and 42 days of administration of Janssen’s replication-incompetent adenoviral vector vaccine were approximately 9 to 12 times higher than after administration of the Pfizer-BioNTech (BNT162b2) or the Moderna (mRNA-1273) mRNA COVID vaccines.

Additionally, observed GBS cases after the Janssen shot were 2 to 3 times greater than expected, based on background rates within 21 and 42 days of vaccination.

Conversely, and confirming prior data, there was no increased risk for GBS with the Pfizer or Moderna vaccines and no significant difference between observed and expected numbers of GBS cases after either mRNA COVID-19 vaccine.

The findings were published online  in JAMA Network Open.
 

More precise risk estimates

Winston Abara, MD, with the U.S. Centers for Disease Control and Prevention, and colleagues analyzed GBS reports submitted to the VAERS between December 2020 and January 2022. 

Among 487.6 million COVID-19 vaccine doses administered, 3.7% were Janssen’s Ad26.COV2.S vaccine, 54.7% were Pfizer’s BNT162b2 vaccine, and 41.6% were Moderna’s mRNA-1273 vaccine.

There were 295 verified reports of GBS identified after COVID-19 vaccination. Of these, 209 occurred within 21 days of vaccination and 253 within 42 days.

Within 21 days of vaccination, GBS reporting rates per 1 million doses were 3.29 for the Janssen vaccine versus 0.29 and 0.35 for the Pfizer and Moderna vaccines, respectively. Within 42 days of vaccination, reporting rates per 1 million doses were 4.07, 0.34, and 0.44, respectively.

Also within 21 days of vaccination, GBS reporting rates were significantly higher with the Janssen vaccine than the Pfizer vaccine (reporting rate ratio, 11.40) and the Moderna vaccine (RRR, 9.26). Similar findings were observed within 42 days after vaccination.

The observed-to-expected ratios were 3.79 for 21-day and 2.34 for 42-day intervals after receipt of the Janssen vaccine, and less than 1 (not significant) after the Pfizer or Moderna vaccine within both post-vaccination periods.

“Unlike prior studies, our analysis included all U.S. reports of verified GBS cases that met the Brighton Collaboration GBS case definition criteria (Brighton Levels 1, 2, and 3) submitted over a 14-month surveillance period to the to the Vaccine Adverse Event Reporting System,” Dr. Abara said in an interview. “Because we used all U.S. reports, the sample of verified GBS cases in this analysis is larger than other studies. Therefore, it may provide a more precise estimate of the GBS risk within 21 and 42 days after mRNA and Ad26.COV2.S vaccination,” he said.
 

‘Remarkably low’ use

Nicola Klein, MD, PhD, Kaiser Permanente Vaccine Study Center, Oakland, Calif., noted that this is a “nice confirmatory analysis that supports and further expands what’s been observed before.”

Last year, as reported by this news organization, Dr. Klein and colleagues reported data from the Vaccine Safety Datalink confirming a small but statistically significant increased risk for GBS in the 3 weeks after receipt of the Janssen COVID-19 vaccine but not the Pfizer or Moderna vaccines.

Unlike VAERS, the Vaccine Safety Datalink is not a reporting system. It’s an active surveillance of medical records in the Kaiser Permanente system. The VAERS is a passive system, so it requires individuals to report GBS cases to the VAERS team, Dr. Klein explained.

So although the two studies are slightly different, overall, the VAERS data is “consistent with what we found,” she said.

Also weighing in, C. Buddy Creech, MD, MPH, director of the Vanderbilt Vaccine Research Program and professor of pediatrics at the Vanderbilt University School of Medicine, Nashville, Tenn., said it is “important to realize that GBS had been observed after adenovirus-vectored vaccines earlier in the pandemic, both for the AstraZeneca vaccine and the Janssen vaccine.”

The Advisory Committee on Immunization Practices (ACIP) preferentially recommends that people age 18 years and older receive an mRNA COVID-19 vaccine rather than the Janssen adenoviral vector vaccine when both types of COVID-19 vaccine are available.

“Thus, the use of the Janssen vaccine is remarkably low in the U.S. right now,” Dr. Creech said.

“Nevertheless, we have a firm commitment, both scientifically and ethically, to track potential side effects after vaccination and to make sure that the vaccines in use for COVID, and other important infectious diseases, are safe and effective,” he added.

The study had no commercial funding. Dr. Abara and Dr. Creech have reported no relevant financial relationships. Dr. Klein reported having received grants from Pfizer research support for a COVID vaccine clinical trial, as well as grants from Merck, GlaxoSmithKline, Sanofi Pasteur, and Protein Science (now Sanofi Pasteur).

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

New surveillance data from the Vaccine Adverse Event Reporting System (VAERS) back previous findings of increased risk for Guillain-Barré syndrome (GBS) after receiving the Janssen COVID-19 vaccine (Ad26.COV2.S).

Over 14 months, GBS reporting rates within 21 and 42 days of administration of Janssen’s replication-incompetent adenoviral vector vaccine were approximately 9 to 12 times higher than after administration of the Pfizer-BioNTech (BNT162b2) or the Moderna (mRNA-1273) mRNA COVID vaccines.

Additionally, observed GBS cases after the Janssen shot were 2 to 3 times greater than expected, based on background rates within 21 and 42 days of vaccination.

Conversely, and confirming prior data, there was no increased risk for GBS with the Pfizer or Moderna vaccines and no significant difference between observed and expected numbers of GBS cases after either mRNA COVID-19 vaccine.

The findings were published online  in JAMA Network Open.
 

More precise risk estimates

Winston Abara, MD, with the U.S. Centers for Disease Control and Prevention, and colleagues analyzed GBS reports submitted to the VAERS between December 2020 and January 2022. 

Among 487.6 million COVID-19 vaccine doses administered, 3.7% were Janssen’s Ad26.COV2.S vaccine, 54.7% were Pfizer’s BNT162b2 vaccine, and 41.6% were Moderna’s mRNA-1273 vaccine.

There were 295 verified reports of GBS identified after COVID-19 vaccination. Of these, 209 occurred within 21 days of vaccination and 253 within 42 days.

Within 21 days of vaccination, GBS reporting rates per 1 million doses were 3.29 for the Janssen vaccine versus 0.29 and 0.35 for the Pfizer and Moderna vaccines, respectively. Within 42 days of vaccination, reporting rates per 1 million doses were 4.07, 0.34, and 0.44, respectively.

Also within 21 days of vaccination, GBS reporting rates were significantly higher with the Janssen vaccine than the Pfizer vaccine (reporting rate ratio, 11.40) and the Moderna vaccine (RRR, 9.26). Similar findings were observed within 42 days after vaccination.

The observed-to-expected ratios were 3.79 for 21-day and 2.34 for 42-day intervals after receipt of the Janssen vaccine, and less than 1 (not significant) after the Pfizer or Moderna vaccine within both post-vaccination periods.

“Unlike prior studies, our analysis included all U.S. reports of verified GBS cases that met the Brighton Collaboration GBS case definition criteria (Brighton Levels 1, 2, and 3) submitted over a 14-month surveillance period to the to the Vaccine Adverse Event Reporting System,” Dr. Abara said in an interview. “Because we used all U.S. reports, the sample of verified GBS cases in this analysis is larger than other studies. Therefore, it may provide a more precise estimate of the GBS risk within 21 and 42 days after mRNA and Ad26.COV2.S vaccination,” he said.
 

‘Remarkably low’ use

Nicola Klein, MD, PhD, Kaiser Permanente Vaccine Study Center, Oakland, Calif., noted that this is a “nice confirmatory analysis that supports and further expands what’s been observed before.”

Last year, as reported by this news organization, Dr. Klein and colleagues reported data from the Vaccine Safety Datalink confirming a small but statistically significant increased risk for GBS in the 3 weeks after receipt of the Janssen COVID-19 vaccine but not the Pfizer or Moderna vaccines.

Unlike VAERS, the Vaccine Safety Datalink is not a reporting system. It’s an active surveillance of medical records in the Kaiser Permanente system. The VAERS is a passive system, so it requires individuals to report GBS cases to the VAERS team, Dr. Klein explained.

So although the two studies are slightly different, overall, the VAERS data is “consistent with what we found,” she said.

Also weighing in, C. Buddy Creech, MD, MPH, director of the Vanderbilt Vaccine Research Program and professor of pediatrics at the Vanderbilt University School of Medicine, Nashville, Tenn., said it is “important to realize that GBS had been observed after adenovirus-vectored vaccines earlier in the pandemic, both for the AstraZeneca vaccine and the Janssen vaccine.”

The Advisory Committee on Immunization Practices (ACIP) preferentially recommends that people age 18 years and older receive an mRNA COVID-19 vaccine rather than the Janssen adenoviral vector vaccine when both types of COVID-19 vaccine are available.

“Thus, the use of the Janssen vaccine is remarkably low in the U.S. right now,” Dr. Creech said.

“Nevertheless, we have a firm commitment, both scientifically and ethically, to track potential side effects after vaccination and to make sure that the vaccines in use for COVID, and other important infectious diseases, are safe and effective,” he added.

The study had no commercial funding. Dr. Abara and Dr. Creech have reported no relevant financial relationships. Dr. Klein reported having received grants from Pfizer research support for a COVID vaccine clinical trial, as well as grants from Merck, GlaxoSmithKline, Sanofi Pasteur, and Protein Science (now Sanofi Pasteur).

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

Nonstop inflammation and immune problems top the list of potential causes of long COVID, but doctors say it’s growing clear that more than one thing is to blame for the wide swath of often debilitating symptoms that could last months or even years.

“I think that it’s a much more complex picture than just inflammation, or just autoimmunity, or just immune dysregulation. And it’s probably a combination of all three causing a cascade of effects that then manifests itself as brain fog, or shortness of breath, or chronic fatigue,” says Alexander Truong, MD, a pulmonologist and assistant professor at Emory University, Atlanta, who also runs a long-COVID clinic.

Long COVID, post–COVID-19 condition, and postacute sequelae of SARS-CoV-2 (PASC) are among the terms used by the National Institutes of Health to describe the long-term health issues faced by an estimated 10%-30% of people infected with COVID-19. Symptoms – as many as 200 – can range from inconvenient to crippling, damage multiple organ systems, come and go, and relapse. Long COVID increases the risk of worsening existing health problems and triggering new ones, including cardiovascular disease and type 2 diabetes.

So far, research suggests there is no single cause, condition, or disease that explains why some people have an extensive range of symptoms long after the early COVID-19 infection has cleared up. Many experts believe some combination of biological processes – including the virus hanging around in our bodies, inflammation, autoimmunity, tiny blood clots, immune system problems, and even the reactivation of dormant viruses such as the Epstein-Barr virus – could be the culprit, a theory also supported by a comprehensive and in-depth review of long-COVID studies published in the journal Nature Reviews Microbiology.

“It’s become clear over the last couple of years that there are different [symptoms] of long COVID … that cannot all be lumped together,” says Michael Peluso, MD, an assistant professor of medicine and an infectious diseases doctor at the University of California, San Francisco.
 

Inflammation and a virus that hangs around

Multiple studies have shown that the virus or pieces of it can remain in many parts of the body, including the kidneys, brain, heart, and gastrointestinal system, long after the early infection. 

“One major question that I think is the area of most intense investigation now is whether there is viral persistence that is driving immune dysregulation and therefore symptoms,” says Dr. Peluso.

A small Harvard University study, for example, found evidence that reservoirs of the coronavirus could linger in patients up to a year after they’re first diagnosed. 

An earlier German study found that patients with post-COVID-19 symptoms had higher levels of three cytokines – small proteins that tell the body’s immune system what to do and are involved in the growth and activity of immune system cells and blood cells. Researchers said the results supported the theory that there is persistent reprogramming of certain immune cells, and that the uncontrolled “self-fueled hyperinflammation” during the early COVID-19 infection can become continued immune cell disruption that drives long-COVID symptoms.

“Long COVID is more likely due to either an inflammatory response by the body or reservoirs of virus that the body is still trying to clear … and the symptoms we’re seeing are a side effect of that,” says Rainu Kaushal, MD, senior associate dean for clinical research at Weill Cornell Medicine in New York.

Australian researchers found that immune system recovery appeared different, compared with those who were infected with other common coronaviruses.

These findings also support concerns that some experts express over the long-term risks of COVID-19 infections in general, but especially repeat infections.

“Anything that kind of revs up inflammation in the body can boil that pot over and make the symptoms worse. That’s very easily an infection or some other insult to the body. So that’s the generalized hypothesis as to why insults to the body may worsen the symptoms,” says Dr. Truong.
 

An autoimmune condition?

But inflammation alone does not fully explain post–COVID-19 problems.

Dr. Truong and his team, for example, have been documenting inflammatory markers in patients at the post-COVID clinic he cofounded more than 2 years ago at Emory Executive Park in Atlanta. When the clinic was first launched, high-dose nonsteroidal anti-inflammatory drugs – including ibuprofen – and prednisone were prescribed to long-COVID patients.

“It didn’t make a difference at all for any of these folks,” he says, adding that there are signs that autoimmunity is at play. But he cautions that it is still too early to suggest treating long-COVID patients with medications used for other autoimmune conditions.

In autoimmune conditions such as rheumatoid arthritis, lupus, and type 1 diabetes, a person’s immune system can’t tell normal cells from foreign pathogens and attacks healthy cells. There is typically no single diagnostic test, and many share similar symptoms, making detection and diagnosis potentially difficult, according to Johns Hopkins Medicine.

A small study published in the journal  Science Translational Medicine found that, among patients who failed to regain their sense of smell long after their initial infection, there was inflammation in the nose tissue where smell nerve cells are found, even though no detectable virus remained. Fewer olfactory sensory neurons were seen, as well – findings that researchers said resembled some kind of “autoimmune-like process.”

Meanwhile, scientists in Canada found signs of autoimmunity in blood samples taken from patients who still had fatigue and shortness of breath after their initial COVID-19 infection. Two specific proteins were present a year after infection in up to 30% of patients, many of whom still had shortness of breath and fatigue, the researchers reported in the Jan. 1 issue of the European Respiratory Journal. These patients had been healthy and had no autoimmune condition or other diseases before they were infected.
 

Immune system problems

A number of studies have suggested that a problematic immune response could also explain why symptoms persist for some people.

Researchers in France, for example, found that the immune response problems in those with severe COVID-19 infections caused exaggerated or uncontrolled formation of a type of bug-fighting defense mechanism called a neutrophil extracellular trap (NET), which in turn triggers harmful inflammation that can result in multiorgan damage. These traps are netlike structures made from fibers composed mostly of DNA strings that bind, or trap, pathogens.

Long COVID is not like an acute infectious disease, says Alexander Charney, MD, PhD, the lead principal investigator of the RECOVER adult cohort at Mount Sinai in New York, and an associate professor at Icahn School of Medicine at Mount Sinai. It is more similar to other complex chronic diseases that have taken decades to understand, such as heart disease, mental illness, and rheumatologic diseases, he says.
 

Biomarkers and blood clots

Scientists are homing in on biomarkers, or detectable and measurable traits – in this case, molecular indicators – that can make diagnosing long COVID easier and give better direction for treatment. These biomarkers are also key to helping sort out the complex biology of long COVID.

In one study, data from blood samples taken from hundreds of hospitalized COVID-19 patients suggests changes are happening at the molecular level during initial severe infections. These changes may be tied to the development of longer-term symptoms, according to the study by Dr. Charney and his team at Mount Sinai published in Nature Medicine

Blood clotting issues have also been detected in long COVID patients. At least one study found signs that long-COVID patients had higher levels of a type of auto-antibody linked to the abnormal formation of clots. Researchers suspect that tiny, persistent microclots – undetectable via regular pathology tests – may be cutting off oxygen flow to tissue by blocking capillaries – and could explain many of the post-COVID symptoms described by patients.

While enormous progress has been made toward understanding long COVID, the research is still considered early and faces many challenges, including varying criteria used to define the condition, the types and quality of data used, differences in how patients are defined and recruited, and the small size of many studies. Some research also appears to conflict with other studies. And while there are specialized tools for diagnosing some aspects of the condition, standard tests often don’t detect many of the signs seen in long-COVID patients. But given the urgency and global scale of the problem, experts say more funding and support should be prioritized.

“People are suffering now, and they want answers now. ... It’s not like with COVID, where the path towards a great and meaningful solution to this unbelievable problem was clear – we need a vaccine,” says Dr. Charney. 

“It’s going to be a long haul to figure out what is going on.”

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

Nonstop inflammation and immune problems top the list of potential causes of long COVID, but doctors say it’s growing clear that more than one thing is to blame for the wide swath of often debilitating symptoms that could last months or even years.

“I think that it’s a much more complex picture than just inflammation, or just autoimmunity, or just immune dysregulation. And it’s probably a combination of all three causing a cascade of effects that then manifests itself as brain fog, or shortness of breath, or chronic fatigue,” says Alexander Truong, MD, a pulmonologist and assistant professor at Emory University, Atlanta, who also runs a long-COVID clinic.

Long COVID, post–COVID-19 condition, and postacute sequelae of SARS-CoV-2 (PASC) are among the terms used by the National Institutes of Health to describe the long-term health issues faced by an estimated 10%-30% of people infected with COVID-19. Symptoms – as many as 200 – can range from inconvenient to crippling, damage multiple organ systems, come and go, and relapse. Long COVID increases the risk of worsening existing health problems and triggering new ones, including cardiovascular disease and type 2 diabetes.

So far, research suggests there is no single cause, condition, or disease that explains why some people have an extensive range of symptoms long after the early COVID-19 infection has cleared up. Many experts believe some combination of biological processes – including the virus hanging around in our bodies, inflammation, autoimmunity, tiny blood clots, immune system problems, and even the reactivation of dormant viruses such as the Epstein-Barr virus – could be the culprit, a theory also supported by a comprehensive and in-depth review of long-COVID studies published in the journal Nature Reviews Microbiology.

“It’s become clear over the last couple of years that there are different [symptoms] of long COVID … that cannot all be lumped together,” says Michael Peluso, MD, an assistant professor of medicine and an infectious diseases doctor at the University of California, San Francisco.
 

Inflammation and a virus that hangs around

Multiple studies have shown that the virus or pieces of it can remain in many parts of the body, including the kidneys, brain, heart, and gastrointestinal system, long after the early infection. 

“One major question that I think is the area of most intense investigation now is whether there is viral persistence that is driving immune dysregulation and therefore symptoms,” says Dr. Peluso.

A small Harvard University study, for example, found evidence that reservoirs of the coronavirus could linger in patients up to a year after they’re first diagnosed. 

An earlier German study found that patients with post-COVID-19 symptoms had higher levels of three cytokines – small proteins that tell the body’s immune system what to do and are involved in the growth and activity of immune system cells and blood cells. Researchers said the results supported the theory that there is persistent reprogramming of certain immune cells, and that the uncontrolled “self-fueled hyperinflammation” during the early COVID-19 infection can become continued immune cell disruption that drives long-COVID symptoms.

“Long COVID is more likely due to either an inflammatory response by the body or reservoirs of virus that the body is still trying to clear … and the symptoms we’re seeing are a side effect of that,” says Rainu Kaushal, MD, senior associate dean for clinical research at Weill Cornell Medicine in New York.

Australian researchers found that immune system recovery appeared different, compared with those who were infected with other common coronaviruses.

These findings also support concerns that some experts express over the long-term risks of COVID-19 infections in general, but especially repeat infections.

“Anything that kind of revs up inflammation in the body can boil that pot over and make the symptoms worse. That’s very easily an infection or some other insult to the body. So that’s the generalized hypothesis as to why insults to the body may worsen the symptoms,” says Dr. Truong.
 

An autoimmune condition?

But inflammation alone does not fully explain post–COVID-19 problems.

Dr. Truong and his team, for example, have been documenting inflammatory markers in patients at the post-COVID clinic he cofounded more than 2 years ago at Emory Executive Park in Atlanta. When the clinic was first launched, high-dose nonsteroidal anti-inflammatory drugs – including ibuprofen – and prednisone were prescribed to long-COVID patients.

“It didn’t make a difference at all for any of these folks,” he says, adding that there are signs that autoimmunity is at play. But he cautions that it is still too early to suggest treating long-COVID patients with medications used for other autoimmune conditions.

In autoimmune conditions such as rheumatoid arthritis, lupus, and type 1 diabetes, a person’s immune system can’t tell normal cells from foreign pathogens and attacks healthy cells. There is typically no single diagnostic test, and many share similar symptoms, making detection and diagnosis potentially difficult, according to Johns Hopkins Medicine.

A small study published in the journal  Science Translational Medicine found that, among patients who failed to regain their sense of smell long after their initial infection, there was inflammation in the nose tissue where smell nerve cells are found, even though no detectable virus remained. Fewer olfactory sensory neurons were seen, as well – findings that researchers said resembled some kind of “autoimmune-like process.”

Meanwhile, scientists in Canada found signs of autoimmunity in blood samples taken from patients who still had fatigue and shortness of breath after their initial COVID-19 infection. Two specific proteins were present a year after infection in up to 30% of patients, many of whom still had shortness of breath and fatigue, the researchers reported in the Jan. 1 issue of the European Respiratory Journal. These patients had been healthy and had no autoimmune condition or other diseases before they were infected.
 

Immune system problems

A number of studies have suggested that a problematic immune response could also explain why symptoms persist for some people.

Researchers in France, for example, found that the immune response problems in those with severe COVID-19 infections caused exaggerated or uncontrolled formation of a type of bug-fighting defense mechanism called a neutrophil extracellular trap (NET), which in turn triggers harmful inflammation that can result in multiorgan damage. These traps are netlike structures made from fibers composed mostly of DNA strings that bind, or trap, pathogens.

Long COVID is not like an acute infectious disease, says Alexander Charney, MD, PhD, the lead principal investigator of the RECOVER adult cohort at Mount Sinai in New York, and an associate professor at Icahn School of Medicine at Mount Sinai. It is more similar to other complex chronic diseases that have taken decades to understand, such as heart disease, mental illness, and rheumatologic diseases, he says.
 

Biomarkers and blood clots

Scientists are homing in on biomarkers, or detectable and measurable traits – in this case, molecular indicators – that can make diagnosing long COVID easier and give better direction for treatment. These biomarkers are also key to helping sort out the complex biology of long COVID.

In one study, data from blood samples taken from hundreds of hospitalized COVID-19 patients suggests changes are happening at the molecular level during initial severe infections. These changes may be tied to the development of longer-term symptoms, according to the study by Dr. Charney and his team at Mount Sinai published in Nature Medicine

Blood clotting issues have also been detected in long COVID patients. At least one study found signs that long-COVID patients had higher levels of a type of auto-antibody linked to the abnormal formation of clots. Researchers suspect that tiny, persistent microclots – undetectable via regular pathology tests – may be cutting off oxygen flow to tissue by blocking capillaries – and could explain many of the post-COVID symptoms described by patients.

While enormous progress has been made toward understanding long COVID, the research is still considered early and faces many challenges, including varying criteria used to define the condition, the types and quality of data used, differences in how patients are defined and recruited, and the small size of many studies. Some research also appears to conflict with other studies. And while there are specialized tools for diagnosing some aspects of the condition, standard tests often don’t detect many of the signs seen in long-COVID patients. But given the urgency and global scale of the problem, experts say more funding and support should be prioritized.

“People are suffering now, and they want answers now. ... It’s not like with COVID, where the path towards a great and meaningful solution to this unbelievable problem was clear – we need a vaccine,” says Dr. Charney. 

“It’s going to be a long haul to figure out what is going on.”

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

Nonstop inflammation and immune problems top the list of potential causes of long COVID, but doctors say it’s growing clear that more than one thing is to blame for the wide swath of often debilitating symptoms that could last months or even years.

“I think that it’s a much more complex picture than just inflammation, or just autoimmunity, or just immune dysregulation. And it’s probably a combination of all three causing a cascade of effects that then manifests itself as brain fog, or shortness of breath, or chronic fatigue,” says Alexander Truong, MD, a pulmonologist and assistant professor at Emory University, Atlanta, who also runs a long-COVID clinic.

Long COVID, post–COVID-19 condition, and postacute sequelae of SARS-CoV-2 (PASC) are among the terms used by the National Institutes of Health to describe the long-term health issues faced by an estimated 10%-30% of people infected with COVID-19. Symptoms – as many as 200 – can range from inconvenient to crippling, damage multiple organ systems, come and go, and relapse. Long COVID increases the risk of worsening existing health problems and triggering new ones, including cardiovascular disease and type 2 diabetes.

So far, research suggests there is no single cause, condition, or disease that explains why some people have an extensive range of symptoms long after the early COVID-19 infection has cleared up. Many experts believe some combination of biological processes – including the virus hanging around in our bodies, inflammation, autoimmunity, tiny blood clots, immune system problems, and even the reactivation of dormant viruses such as the Epstein-Barr virus – could be the culprit, a theory also supported by a comprehensive and in-depth review of long-COVID studies published in the journal Nature Reviews Microbiology.

“It’s become clear over the last couple of years that there are different [symptoms] of long COVID … that cannot all be lumped together,” says Michael Peluso, MD, an assistant professor of medicine and an infectious diseases doctor at the University of California, San Francisco.
 

Inflammation and a virus that hangs around

Multiple studies have shown that the virus or pieces of it can remain in many parts of the body, including the kidneys, brain, heart, and gastrointestinal system, long after the early infection. 

“One major question that I think is the area of most intense investigation now is whether there is viral persistence that is driving immune dysregulation and therefore symptoms,” says Dr. Peluso.

A small Harvard University study, for example, found evidence that reservoirs of the coronavirus could linger in patients up to a year after they’re first diagnosed. 

An earlier German study found that patients with post-COVID-19 symptoms had higher levels of three cytokines – small proteins that tell the body’s immune system what to do and are involved in the growth and activity of immune system cells and blood cells. Researchers said the results supported the theory that there is persistent reprogramming of certain immune cells, and that the uncontrolled “self-fueled hyperinflammation” during the early COVID-19 infection can become continued immune cell disruption that drives long-COVID symptoms.

“Long COVID is more likely due to either an inflammatory response by the body or reservoirs of virus that the body is still trying to clear … and the symptoms we’re seeing are a side effect of that,” says Rainu Kaushal, MD, senior associate dean for clinical research at Weill Cornell Medicine in New York.

Australian researchers found that immune system recovery appeared different, compared with those who were infected with other common coronaviruses.

These findings also support concerns that some experts express over the long-term risks of COVID-19 infections in general, but especially repeat infections.

“Anything that kind of revs up inflammation in the body can boil that pot over and make the symptoms worse. That’s very easily an infection or some other insult to the body. So that’s the generalized hypothesis as to why insults to the body may worsen the symptoms,” says Dr. Truong.
 

An autoimmune condition?

But inflammation alone does not fully explain post–COVID-19 problems.

Dr. Truong and his team, for example, have been documenting inflammatory markers in patients at the post-COVID clinic he cofounded more than 2 years ago at Emory Executive Park in Atlanta. When the clinic was first launched, high-dose nonsteroidal anti-inflammatory drugs – including ibuprofen – and prednisone were prescribed to long-COVID patients.

“It didn’t make a difference at all for any of these folks,” he says, adding that there are signs that autoimmunity is at play. But he cautions that it is still too early to suggest treating long-COVID patients with medications used for other autoimmune conditions.

In autoimmune conditions such as rheumatoid arthritis, lupus, and type 1 diabetes, a person’s immune system can’t tell normal cells from foreign pathogens and attacks healthy cells. There is typically no single diagnostic test, and many share similar symptoms, making detection and diagnosis potentially difficult, according to Johns Hopkins Medicine.

A small study published in the journal  Science Translational Medicine found that, among patients who failed to regain their sense of smell long after their initial infection, there was inflammation in the nose tissue where smell nerve cells are found, even though no detectable virus remained. Fewer olfactory sensory neurons were seen, as well – findings that researchers said resembled some kind of “autoimmune-like process.”

Meanwhile, scientists in Canada found signs of autoimmunity in blood samples taken from patients who still had fatigue and shortness of breath after their initial COVID-19 infection. Two specific proteins were present a year after infection in up to 30% of patients, many of whom still had shortness of breath and fatigue, the researchers reported in the Jan. 1 issue of the European Respiratory Journal. These patients had been healthy and had no autoimmune condition or other diseases before they were infected.
 

Immune system problems

A number of studies have suggested that a problematic immune response could also explain why symptoms persist for some people.

Researchers in France, for example, found that the immune response problems in those with severe COVID-19 infections caused exaggerated or uncontrolled formation of a type of bug-fighting defense mechanism called a neutrophil extracellular trap (NET), which in turn triggers harmful inflammation that can result in multiorgan damage. These traps are netlike structures made from fibers composed mostly of DNA strings that bind, or trap, pathogens.

Long COVID is not like an acute infectious disease, says Alexander Charney, MD, PhD, the lead principal investigator of the RECOVER adult cohort at Mount Sinai in New York, and an associate professor at Icahn School of Medicine at Mount Sinai. It is more similar to other complex chronic diseases that have taken decades to understand, such as heart disease, mental illness, and rheumatologic diseases, he says.
 

Biomarkers and blood clots

Scientists are homing in on biomarkers, or detectable and measurable traits – in this case, molecular indicators – that can make diagnosing long COVID easier and give better direction for treatment. These biomarkers are also key to helping sort out the complex biology of long COVID.

In one study, data from blood samples taken from hundreds of hospitalized COVID-19 patients suggests changes are happening at the molecular level during initial severe infections. These changes may be tied to the development of longer-term symptoms, according to the study by Dr. Charney and his team at Mount Sinai published in Nature Medicine

Blood clotting issues have also been detected in long COVID patients. At least one study found signs that long-COVID patients had higher levels of a type of auto-antibody linked to the abnormal formation of clots. Researchers suspect that tiny, persistent microclots – undetectable via regular pathology tests – may be cutting off oxygen flow to tissue by blocking capillaries – and could explain many of the post-COVID symptoms described by patients.

While enormous progress has been made toward understanding long COVID, the research is still considered early and faces many challenges, including varying criteria used to define the condition, the types and quality of data used, differences in how patients are defined and recruited, and the small size of many studies. Some research also appears to conflict with other studies. And while there are specialized tools for diagnosing some aspects of the condition, standard tests often don’t detect many of the signs seen in long-COVID patients. But given the urgency and global scale of the problem, experts say more funding and support should be prioritized.

“People are suffering now, and they want answers now. ... It’s not like with COVID, where the path towards a great and meaningful solution to this unbelievable problem was clear – we need a vaccine,” says Dr. Charney. 

“It’s going to be a long haul to figure out what is going on.”

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

Almost 36% of students and faculty at George Washington University with a history of COVID-19 reported symptoms consistent with long COVID in a new study.

With a median age of 23 years, the study is unique for evaluating mostly healthy, young adults and for its rare look at long COVID in a university community. 

The more symptoms during a bout with COVID, the greater the risk for long COVID, the researchers found. That lines up with previous studies. Also, the more vaccinations and booster shots against SARS-CoV-2, the virus that causes COVID, the lower the long COVID risk.

Women were more likely than men to be affected. Current or prior smoking, seeking medical care for COVID, and receiving antibody treatment also were linked to higher chances for developing long COVID. 

Lead author Megan Landry, DrPH, MPH, and colleagues were already assessing students, staff, and faculty at George Washington University, Washington, who tested positive for COVID. Then they started seeing symptoms that lasted 28 days or more after their 10-day isolation period. 

“We were starting to recognize that individuals ... were still having symptoms longer than the typical isolation period,” said Dr. Landry. So they developed a questionnaire to figure out the how long these symptoms last and how many people are affected by them. 

The list of potential symptoms was long and included trouble thinking, fatigue, loss of smell or taste, shortness of breath, and more. 

The study was published online in Emerging Infectious Diseases. Results are based on records and responses from 1,388 students, faculty, and staff from July 2021 to March 2022.

People had a median of four long COVID symptoms, about 63% were women, and 56% were non-Hispanic White. About three-quarters were students and the remainder were faculty and staff. 

The finding that 36% of people with a history of COVID reported long COVID symptoms did not surprise Dr. Landry.

“Based on the literature that’s currently out there, it ranges from a 10% to an 80% prevalence of long COVID,” she said. “We kind of figured that we would fall somewhere in there.”

In contrast, that figure seemed high to Eric Topol, MD.

“That’s really high,” said Dr. Topol, founder and director of the Scripps Research Translational Institute in La Jolla, Calif. He added most studies estimate that about 10% of people with a history of acute infection develop long COVID. 

Even at 10%, which could be an underestimate, that’s a lot of affected people globally. 

“At least 65 million individuals around the world have long COVID, based on a conservative estimated incidence of 10% of infected people and more than 651 million documented COVID-19 cases worldwide; the number is likely much higher due to many undocumented cases,” Dr. Topol and colleagues wrote in a long COVID review article published in Nature Reviews Microbiology.

Research continues

“Long COVID is still evolving and we continue to learn more about it every day,” Landry said. “It’s just so new and there are still a lot of unknowns. That’s why it’s important to get this information out.” 

People with long COVID often have a hard time with occupational, educational, social, or personal activities, compared with before COVID, with effects that can last for more than 6 months, the authors noted. 

“I think across the board, universities in general need to consider the possibility of folks on their campuses are having symptoms of long COVID,” Dr. Landry said.

Moving forward, Dr. Landry and colleagues would like to continue investigating long COVID. For example, in the current study, they did not ask about severity of symptoms or how the symptoms affected daily functioning. 

“I would like to continue this and dive deeper into how disruptive their symptoms of long COVID are to their everyday studying, teaching, or their activities to keeping a university running,” Dr. Landry said.

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

Almost 36% of students and faculty at George Washington University with a history of COVID-19 reported symptoms consistent with long COVID in a new study.

With a median age of 23 years, the study is unique for evaluating mostly healthy, young adults and for its rare look at long COVID in a university community. 

The more symptoms during a bout with COVID, the greater the risk for long COVID, the researchers found. That lines up with previous studies. Also, the more vaccinations and booster shots against SARS-CoV-2, the virus that causes COVID, the lower the long COVID risk.

Women were more likely than men to be affected. Current or prior smoking, seeking medical care for COVID, and receiving antibody treatment also were linked to higher chances for developing long COVID. 

Lead author Megan Landry, DrPH, MPH, and colleagues were already assessing students, staff, and faculty at George Washington University, Washington, who tested positive for COVID. Then they started seeing symptoms that lasted 28 days or more after their 10-day isolation period. 

“We were starting to recognize that individuals ... were still having symptoms longer than the typical isolation period,” said Dr. Landry. So they developed a questionnaire to figure out the how long these symptoms last and how many people are affected by them. 

The list of potential symptoms was long and included trouble thinking, fatigue, loss of smell or taste, shortness of breath, and more. 

The study was published online in Emerging Infectious Diseases. Results are based on records and responses from 1,388 students, faculty, and staff from July 2021 to March 2022.

People had a median of four long COVID symptoms, about 63% were women, and 56% were non-Hispanic White. About three-quarters were students and the remainder were faculty and staff. 

The finding that 36% of people with a history of COVID reported long COVID symptoms did not surprise Dr. Landry.

“Based on the literature that’s currently out there, it ranges from a 10% to an 80% prevalence of long COVID,” she said. “We kind of figured that we would fall somewhere in there.”

In contrast, that figure seemed high to Eric Topol, MD.

“That’s really high,” said Dr. Topol, founder and director of the Scripps Research Translational Institute in La Jolla, Calif. He added most studies estimate that about 10% of people with a history of acute infection develop long COVID. 

Even at 10%, which could be an underestimate, that’s a lot of affected people globally. 

“At least 65 million individuals around the world have long COVID, based on a conservative estimated incidence of 10% of infected people and more than 651 million documented COVID-19 cases worldwide; the number is likely much higher due to many undocumented cases,” Dr. Topol and colleagues wrote in a long COVID review article published in Nature Reviews Microbiology.

Research continues

“Long COVID is still evolving and we continue to learn more about it every day,” Landry said. “It’s just so new and there are still a lot of unknowns. That’s why it’s important to get this information out.” 

People with long COVID often have a hard time with occupational, educational, social, or personal activities, compared with before COVID, with effects that can last for more than 6 months, the authors noted. 

“I think across the board, universities in general need to consider the possibility of folks on their campuses are having symptoms of long COVID,” Dr. Landry said.

Moving forward, Dr. Landry and colleagues would like to continue investigating long COVID. For example, in the current study, they did not ask about severity of symptoms or how the symptoms affected daily functioning. 

“I would like to continue this and dive deeper into how disruptive their symptoms of long COVID are to their everyday studying, teaching, or their activities to keeping a university running,” Dr. Landry said.

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

Almost 36% of students and faculty at George Washington University with a history of COVID-19 reported symptoms consistent with long COVID in a new study.

With a median age of 23 years, the study is unique for evaluating mostly healthy, young adults and for its rare look at long COVID in a university community. 

The more symptoms during a bout with COVID, the greater the risk for long COVID, the researchers found. That lines up with previous studies. Also, the more vaccinations and booster shots against SARS-CoV-2, the virus that causes COVID, the lower the long COVID risk.

Women were more likely than men to be affected. Current or prior smoking, seeking medical care for COVID, and receiving antibody treatment also were linked to higher chances for developing long COVID. 

Lead author Megan Landry, DrPH, MPH, and colleagues were already assessing students, staff, and faculty at George Washington University, Washington, who tested positive for COVID. Then they started seeing symptoms that lasted 28 days or more after their 10-day isolation period. 

“We were starting to recognize that individuals ... were still having symptoms longer than the typical isolation period,” said Dr. Landry. So they developed a questionnaire to figure out the how long these symptoms last and how many people are affected by them. 

The list of potential symptoms was long and included trouble thinking, fatigue, loss of smell or taste, shortness of breath, and more. 

The study was published online in Emerging Infectious Diseases. Results are based on records and responses from 1,388 students, faculty, and staff from July 2021 to March 2022.

People had a median of four long COVID symptoms, about 63% were women, and 56% were non-Hispanic White. About three-quarters were students and the remainder were faculty and staff. 

The finding that 36% of people with a history of COVID reported long COVID symptoms did not surprise Dr. Landry.

“Based on the literature that’s currently out there, it ranges from a 10% to an 80% prevalence of long COVID,” she said. “We kind of figured that we would fall somewhere in there.”

In contrast, that figure seemed high to Eric Topol, MD.

“That’s really high,” said Dr. Topol, founder and director of the Scripps Research Translational Institute in La Jolla, Calif. He added most studies estimate that about 10% of people with a history of acute infection develop long COVID. 

Even at 10%, which could be an underestimate, that’s a lot of affected people globally. 

“At least 65 million individuals around the world have long COVID, based on a conservative estimated incidence of 10% of infected people and more than 651 million documented COVID-19 cases worldwide; the number is likely much higher due to many undocumented cases,” Dr. Topol and colleagues wrote in a long COVID review article published in Nature Reviews Microbiology.

Research continues

“Long COVID is still evolving and we continue to learn more about it every day,” Landry said. “It’s just so new and there are still a lot of unknowns. That’s why it’s important to get this information out.” 

People with long COVID often have a hard time with occupational, educational, social, or personal activities, compared with before COVID, with effects that can last for more than 6 months, the authors noted. 

“I think across the board, universities in general need to consider the possibility of folks on their campuses are having symptoms of long COVID,” Dr. Landry said.

Moving forward, Dr. Landry and colleagues would like to continue investigating long COVID. For example, in the current study, they did not ask about severity of symptoms or how the symptoms affected daily functioning. 

“I would like to continue this and dive deeper into how disruptive their symptoms of long COVID are to their everyday studying, teaching, or their activities to keeping a university running,” Dr. Landry said.

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

U.S. health officials want to simplify the recommended COVID-19 vaccine protocol, making it more like the process for annual flu shots.

The U.S. Food and Drug Administration is suggesting a single annual shot. The formulation would be selected in June targeting the most threatening COVID-19 strains, and then people could get a shot in the fall when people begin spending more time indoors and exposure increases. 

Some people, such as those who are older or immunocompromised, may need more than one dose.

A national advisory committee is expected to vote on the proposal at a meeting Jan. 26.

People in the United States have been much less likely to get an updated COVID-19 booster shot, compared with widespread uptake of the primary vaccine series. In its proposal, the FDA indicated it hoped a single annual shot would overcome challenges created by the complexity of the process – both in messaging and administration – attributed to that low booster rate. Nine in 10 people age 12 or older got the primary vaccine series in the United States, but only 15% got the latest booster shot for COVID-19.

About half of children and adults in the U.S. get an annual flu shot, according to Centers for Disease Control and Prevention data.

The FDA also wants to move to a single COVID-19 vaccine formulation that would be used for primary vaccine series and for booster shots.

COVID-19 cases, hospitalizations, and deaths are trending downward, according to the data tracker from the New York Times. Cases are down 28%, with 47,290 tallied daily. Hospitalizations are down 22%, with 37,474 daily. Deaths are down 4%, with an average of 489 per day as of Jan. 22.

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

U.S. health officials want to simplify the recommended COVID-19 vaccine protocol, making it more like the process for annual flu shots.

The U.S. Food and Drug Administration is suggesting a single annual shot. The formulation would be selected in June targeting the most threatening COVID-19 strains, and then people could get a shot in the fall when people begin spending more time indoors and exposure increases. 

Some people, such as those who are older or immunocompromised, may need more than one dose.

A national advisory committee is expected to vote on the proposal at a meeting Jan. 26.

People in the United States have been much less likely to get an updated COVID-19 booster shot, compared with widespread uptake of the primary vaccine series. In its proposal, the FDA indicated it hoped a single annual shot would overcome challenges created by the complexity of the process – both in messaging and administration – attributed to that low booster rate. Nine in 10 people age 12 or older got the primary vaccine series in the United States, but only 15% got the latest booster shot for COVID-19.

About half of children and adults in the U.S. get an annual flu shot, according to Centers for Disease Control and Prevention data.

The FDA also wants to move to a single COVID-19 vaccine formulation that would be used for primary vaccine series and for booster shots.

COVID-19 cases, hospitalizations, and deaths are trending downward, according to the data tracker from the New York Times. Cases are down 28%, with 47,290 tallied daily. Hospitalizations are down 22%, with 37,474 daily. Deaths are down 4%, with an average of 489 per day as of Jan. 22.

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

U.S. health officials want to simplify the recommended COVID-19 vaccine protocol, making it more like the process for annual flu shots.

The U.S. Food and Drug Administration is suggesting a single annual shot. The formulation would be selected in June targeting the most threatening COVID-19 strains, and then people could get a shot in the fall when people begin spending more time indoors and exposure increases. 

Some people, such as those who are older or immunocompromised, may need more than one dose.

A national advisory committee is expected to vote on the proposal at a meeting Jan. 26.

People in the United States have been much less likely to get an updated COVID-19 booster shot, compared with widespread uptake of the primary vaccine series. In its proposal, the FDA indicated it hoped a single annual shot would overcome challenges created by the complexity of the process – both in messaging and administration – attributed to that low booster rate. Nine in 10 people age 12 or older got the primary vaccine series in the United States, but only 15% got the latest booster shot for COVID-19.

About half of children and adults in the U.S. get an annual flu shot, according to Centers for Disease Control and Prevention data.

The FDA also wants to move to a single COVID-19 vaccine formulation that would be used for primary vaccine series and for booster shots.

COVID-19 cases, hospitalizations, and deaths are trending downward, according to the data tracker from the New York Times. Cases are down 28%, with 47,290 tallied daily. Hospitalizations are down 22%, with 37,474 daily. Deaths are down 4%, with an average of 489 per day as of Jan. 22.

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

The only HIV vaccine nearing the completion of testing trials is not effective at preventing HIV, officials announced Wednesday.

The vaccine had been in development since 2019 and was given to 3,900 study participants through October 2022, but data shows it does not protect against HIV compared with a placebo, according to developer Janssen Pharmaceutical.

Experts estimate the failure means there won’t be another potential vaccine on the horizon for 3 to 5 years, the New York Times reported.

“It’s obviously disappointing,” Anthony Fauci, MD, former head of the National Institute of Allergy and Infectious Diseases, told MSNBC, noting that other areas of HIV treatment research are promising. “I don’t think that people should give up on the field of the HIV vaccine.”

No safety issues had been identified with the vaccine during the trial, which studied the experimental treatment in men who have sex with men or with transgender people.

There is no cure for HIV, but disease progression can be managed with existing treatments. HIV attacks the body’s immune system and destroys white blood cells, increasing the risk of other infections. More than 1.5 million people worldwide were infected with HIV in 2021 and 38.4 million people are living with the virus, according to UNAIDS.

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

The only HIV vaccine nearing the completion of testing trials is not effective at preventing HIV, officials announced Wednesday.

The vaccine had been in development since 2019 and was given to 3,900 study participants through October 2022, but data shows it does not protect against HIV compared with a placebo, according to developer Janssen Pharmaceutical.

Experts estimate the failure means there won’t be another potential vaccine on the horizon for 3 to 5 years, the New York Times reported.

“It’s obviously disappointing,” Anthony Fauci, MD, former head of the National Institute of Allergy and Infectious Diseases, told MSNBC, noting that other areas of HIV treatment research are promising. “I don’t think that people should give up on the field of the HIV vaccine.”

No safety issues had been identified with the vaccine during the trial, which studied the experimental treatment in men who have sex with men or with transgender people.

There is no cure for HIV, but disease progression can be managed with existing treatments. HIV attacks the body’s immune system and destroys white blood cells, increasing the risk of other infections. More than 1.5 million people worldwide were infected with HIV in 2021 and 38.4 million people are living with the virus, according to UNAIDS.

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

The only HIV vaccine nearing the completion of testing trials is not effective at preventing HIV, officials announced Wednesday.

The vaccine had been in development since 2019 and was given to 3,900 study participants through October 2022, but data shows it does not protect against HIV compared with a placebo, according to developer Janssen Pharmaceutical.

Experts estimate the failure means there won’t be another potential vaccine on the horizon for 3 to 5 years, the New York Times reported.

“It’s obviously disappointing,” Anthony Fauci, MD, former head of the National Institute of Allergy and Infectious Diseases, told MSNBC, noting that other areas of HIV treatment research are promising. “I don’t think that people should give up on the field of the HIV vaccine.”

No safety issues had been identified with the vaccine during the trial, which studied the experimental treatment in men who have sex with men or with transgender people.

There is no cure for HIV, but disease progression can be managed with existing treatments. HIV attacks the body’s immune system and destroys white blood cells, increasing the risk of other infections. More than 1.5 million people worldwide were infected with HIV in 2021 and 38.4 million people are living with the virus, according to UNAIDS.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

It was the last monoclonal antibody treatment standing. But less than 10 months after the U.S. Food and Drug Administration gave bebtelovimab its emergency use authorization (EUA) to fight COVID-19, it earlier this month de-authorized it, just as it had for other monoclonal antibody treatments, and for the same reason: The treatments were outwitted by the viral mutations.
 

Bebtelovimab couldn’t neutralize the Omicron subvariants BQ.1 and BQ.1.1, the cause of nearly 60% of COVID cases nationally as of November 30.

Next on the chopping block, some predict, will be Evusheld, the combination of tixagevimab and cilgavimab given as a preventive monoclonal antibody to people who are immunocompromised and at high risk of contracting COVID and to those who can’t take the vaccine. In October, the FDA warned that Evusheld was not neutralizing circulating COVID variants.

As the options for treating and preventing COVID decline, will companies rally quickly to develop new ones, or cut their losses in developing treatments that may work for only a few months, given the speed of viral mutations?

But although monoclonal antibody treatments are off the table, at least for now, antiviral drugs – including Paxlovid – are still very much available, and some say underused.

Others suggest it’s time to resurrect interest in convalescent plasma, a treatment used early in the pandemic before drugs or vaccines were here and still authorized for use in those who are immunosuppressed or receiving immunosuppressive treatment.

And on the prevention front, staying up to date with booster vaccines, masking, and taking other precautions should be stressed more, others say, regardless of the number of treatment options, and especially now, as cases rise and people gather for the winter holidays.
 

‘A major setback’

The bebtelovimab de-authorization was “a major setback,” but an understandable one, said Arturo Casadevall, MD, PhD, professor and chair of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health in Baltimore. “Monoclonal antibodies are great drugs. We are in an unfortunate situation in that they are vulnerable to changes in the virus” and can’t offer long-lasting protection.

Supplies of bebtelovimab will be retained, according to the FDA, in case variants susceptible to it return.

“What happened to bebtelovimab is no surprise,” agreed Amesh Adalja, MD, senior scholar at Johns Hopkins Center for Health Security. “This is what is going to happen when you are targeting a virus that mutates a lot.”

Monoclonal antibodies work by binding to the spike protein on the virus surface to prevent it from entering cells.

However, Dr. Adalja doesn’t view the disappearance of monoclonal antibody treatments as a major setback. Monoclonal antibodies were not the primary way COVID was treated, he said.

While he does believe it’s important that more monoclonal antibody treatments be developed, “I think it’s important to remember we still have Paxlovid while everyone is lamenting the loss of bebtelovimab.’’
 

Antivirals: What’s here, what’s coming

Compared with monoclonal antibodies, “Paxlovid remains a much easier drug to give,” Dr. Adalja told this news organization, because it is taken orally, not intravenously.

And it’s effective. In a recent study, researchers found that adults diagnosed with COVID given Paxlovid within 5 days of diagnosis had a 51% lower hospitalization rate within the next 30 days than those not given it. Another study shows it could also reduce a person’s risk of developing long COVID by 26%.

Paxlovid is underused, Dr. Adalja said, partly because the rebound potential got more press than the effectiveness. When a celebrity got rebound from Paxlovid, he said, that would make the news, overshadowing the research on its effectiveness.

Besides Paxlovid, the antivirals remdesivir (Veklury), given intravenously for 3 days, and molnupiravir (Lagevrio), taken orally, are also still available. Antivirals work by targeting specific parts of the virus to prevent it from multiplying.

In the lab, remdesivir, molnupiravir, and another antiviral, nirmatrelvir, all appear to be effective against both BQ.1.1 (a BA.5 subvariant) and XBB (a BA.2 subvariant), both rapidly rising in the United States, according to a report last week in the New England Journal of Medicine.

The researchers also tested several monoclonal antibodies and found they did not neutralize either of the subvariants BQ.1.1 and XBB.

A new oral antiviral, Xocova (ensitrelvir fumaric acid), from Japanese manufacturer Shionogi, received emergency approval in Japan on November 22. It’s taken once a day for 5 days. The goal is to expand access to it globally, according to the company.

Pardes Biosciences launched a phase 2 trial in September for its oral antiviral drug (PBI-0451), under study as a treatment and preventive for COVID. It expects data by the first quarter of 2023.

Pfizer, which makes Paxlovid, has partnered with Clear Creek Bio to develop another oral antiviral COVID drug.
 

Other approaches

A receptor protein known as ACE2 (angiotensin-converting enzyme 2) is the main “doorway” that SARS-CoV-2 uses to enter and infect cells.

Dana-Farber Cancer Institute scientists are developing a “decoy” drug that works by mimicking the ACE2 receptor on the surface of cells; when the virus tries to bind to it, the spike protein is destroyed. Human trials have not yet started.

Other researchers are investigating whether an already-approved drug used to treat a liver disease, Actigall (UDCA/ursodeoxycholic acid), could protect against COVID infection by reducing ACE2.

So far, the researchers have found in early research that people taking UDCA for liver conditions were less likely than those not taking the drug to have severe COVID. They also found that UDCA reduced SARS-CoV-2 infection in human lungs maintained outside the body.
 

Monoclonal antibody treatments?

After the FDA decision to withdraw the bebtelovimab EUA, which Eli Lilly said it agreed with, the company issued a statement, promising it wasn’t giving up on monoclonal antibody treatments.

“Lilly will continue to search and evaluate monoclonal antibodies to identify potential candidates for clinical development against new variants,” it read in part.

AstraZeneca, which makes Evusheld, is also continuing to work on monoclonal antibody development. According to a spokesperson, “We are also developing a new long-acting antibody combination – AZD5156 – which has been shown in the lab to neutralize emerging new variants and all known variants to date. We are working to accelerate the development of AZD5156 to make it available at the end of 2023.”

The AstraZeneca spokesperson said he could share no more information about what the combination would include.
 

A convalescent plasma comeback?

Although Paxlovid can help, there are many contraindications to it, such as drug-drug interactions, Dr. Casadevall told this news organization. And now that the monoclonal antibody treatments have been paused, convalescent plasma “is the only antibody-based therapy that is reliably available. Convalescent plasma includes thousands of different antibodies.”

With his colleagues, Dr. Casadevall evaluated plasma samples from 740 patients. Some had received booster vaccines and been infected with Omicron, others had received boosters and not been infected, and still others had not been vaccinated and became infected.

In a report (not yet peer-reviewed), they found the plasma from those who had been infected or boosted within the past 6 months neutralized the new Omicron variants BQ.1.1, XBB.1, and BF.7.
 

A push for boosters, masks

To get through the coming months, taking precautions like masking and distancing and staying up to date on booster vaccinations, especially for older adults, can make a difference, other experts say.

In a Twitter thread in early December, Peter Hotez, MD, PhD, professor of pediatrics and molecular virology and microbiology at Baylor College of Medicine, Houston, urged people to take COVID seriously as holiday parties and gatherings occur.

“The single most impactful thing you can do is get your bivalent booster,” he tweeted, as well as give your kids the booster, citing preliminary research that the bivalent mRNA booster broadens immunity against the Omicron subvariants.

For seniors, he said, ‘‘if you get breakthrough COVID, [it’s] really important to get Paxlovid.” Masks will help not only for COVID but also influenza, respiratory syncytial virus (RSV), and other conditions.

Mitigation measures have largely been abandoned, according to Eric Topol, MD, director of the Scripps Research Translational Institute, La Jolla, Calif., and editor-in-chief of Medscape. In an op-ed in the Los Angeles Times, and on his Twitter feed, he reminds people about masking and urges people to get the bivalent booster.

According to the Centers for Disease Control and Prevention, as of Dec. 8, only 13.5% of people aged 5 and older have gotten an updated booster, despite research that shows an increase in antibodies to BQ.1.1. Recent research has found that the bivalent booster increases antibodies to BQ.1.1 by up to 10-fold, Dr. Topol said.

Dr. Adalja is on advisory boards for Shionogi, GSK, and Pardes. Dr. Casadevall reports no relevant financial relationships.

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

It was the last monoclonal antibody treatment standing. But less than 10 months after the U.S. Food and Drug Administration gave bebtelovimab its emergency use authorization (EUA) to fight COVID-19, it earlier this month de-authorized it, just as it had for other monoclonal antibody treatments, and for the same reason: The treatments were outwitted by the viral mutations.
 

Bebtelovimab couldn’t neutralize the Omicron subvariants BQ.1 and BQ.1.1, the cause of nearly 60% of COVID cases nationally as of November 30.

Next on the chopping block, some predict, will be Evusheld, the combination of tixagevimab and cilgavimab given as a preventive monoclonal antibody to people who are immunocompromised and at high risk of contracting COVID and to those who can’t take the vaccine. In October, the FDA warned that Evusheld was not neutralizing circulating COVID variants.

As the options for treating and preventing COVID decline, will companies rally quickly to develop new ones, or cut their losses in developing treatments that may work for only a few months, given the speed of viral mutations?

But although monoclonal antibody treatments are off the table, at least for now, antiviral drugs – including Paxlovid – are still very much available, and some say underused.

Others suggest it’s time to resurrect interest in convalescent plasma, a treatment used early in the pandemic before drugs or vaccines were here and still authorized for use in those who are immunosuppressed or receiving immunosuppressive treatment.

And on the prevention front, staying up to date with booster vaccines, masking, and taking other precautions should be stressed more, others say, regardless of the number of treatment options, and especially now, as cases rise and people gather for the winter holidays.
 

‘A major setback’

The bebtelovimab de-authorization was “a major setback,” but an understandable one, said Arturo Casadevall, MD, PhD, professor and chair of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health in Baltimore. “Monoclonal antibodies are great drugs. We are in an unfortunate situation in that they are vulnerable to changes in the virus” and can’t offer long-lasting protection.

Supplies of bebtelovimab will be retained, according to the FDA, in case variants susceptible to it return.

“What happened to bebtelovimab is no surprise,” agreed Amesh Adalja, MD, senior scholar at Johns Hopkins Center for Health Security. “This is what is going to happen when you are targeting a virus that mutates a lot.”

Monoclonal antibodies work by binding to the spike protein on the virus surface to prevent it from entering cells.

However, Dr. Adalja doesn’t view the disappearance of monoclonal antibody treatments as a major setback. Monoclonal antibodies were not the primary way COVID was treated, he said.

While he does believe it’s important that more monoclonal antibody treatments be developed, “I think it’s important to remember we still have Paxlovid while everyone is lamenting the loss of bebtelovimab.’’
 

Antivirals: What’s here, what’s coming

Compared with monoclonal antibodies, “Paxlovid remains a much easier drug to give,” Dr. Adalja told this news organization, because it is taken orally, not intravenously.

And it’s effective. In a recent study, researchers found that adults diagnosed with COVID given Paxlovid within 5 days of diagnosis had a 51% lower hospitalization rate within the next 30 days than those not given it. Another study shows it could also reduce a person’s risk of developing long COVID by 26%.

Paxlovid is underused, Dr. Adalja said, partly because the rebound potential got more press than the effectiveness. When a celebrity got rebound from Paxlovid, he said, that would make the news, overshadowing the research on its effectiveness.

Besides Paxlovid, the antivirals remdesivir (Veklury), given intravenously for 3 days, and molnupiravir (Lagevrio), taken orally, are also still available. Antivirals work by targeting specific parts of the virus to prevent it from multiplying.

In the lab, remdesivir, molnupiravir, and another antiviral, nirmatrelvir, all appear to be effective against both BQ.1.1 (a BA.5 subvariant) and XBB (a BA.2 subvariant), both rapidly rising in the United States, according to a report last week in the New England Journal of Medicine.

The researchers also tested several monoclonal antibodies and found they did not neutralize either of the subvariants BQ.1.1 and XBB.

A new oral antiviral, Xocova (ensitrelvir fumaric acid), from Japanese manufacturer Shionogi, received emergency approval in Japan on November 22. It’s taken once a day for 5 days. The goal is to expand access to it globally, according to the company.

Pardes Biosciences launched a phase 2 trial in September for its oral antiviral drug (PBI-0451), under study as a treatment and preventive for COVID. It expects data by the first quarter of 2023.

Pfizer, which makes Paxlovid, has partnered with Clear Creek Bio to develop another oral antiviral COVID drug.
 

Other approaches

A receptor protein known as ACE2 (angiotensin-converting enzyme 2) is the main “doorway” that SARS-CoV-2 uses to enter and infect cells.

Dana-Farber Cancer Institute scientists are developing a “decoy” drug that works by mimicking the ACE2 receptor on the surface of cells; when the virus tries to bind to it, the spike protein is destroyed. Human trials have not yet started.

Other researchers are investigating whether an already-approved drug used to treat a liver disease, Actigall (UDCA/ursodeoxycholic acid), could protect against COVID infection by reducing ACE2.

So far, the researchers have found in early research that people taking UDCA for liver conditions were less likely than those not taking the drug to have severe COVID. They also found that UDCA reduced SARS-CoV-2 infection in human lungs maintained outside the body.
 

Monoclonal antibody treatments?

After the FDA decision to withdraw the bebtelovimab EUA, which Eli Lilly said it agreed with, the company issued a statement, promising it wasn’t giving up on monoclonal antibody treatments.

“Lilly will continue to search and evaluate monoclonal antibodies to identify potential candidates for clinical development against new variants,” it read in part.

AstraZeneca, which makes Evusheld, is also continuing to work on monoclonal antibody development. According to a spokesperson, “We are also developing a new long-acting antibody combination – AZD5156 – which has been shown in the lab to neutralize emerging new variants and all known variants to date. We are working to accelerate the development of AZD5156 to make it available at the end of 2023.”

The AstraZeneca spokesperson said he could share no more information about what the combination would include.
 

A convalescent plasma comeback?

Although Paxlovid can help, there are many contraindications to it, such as drug-drug interactions, Dr. Casadevall told this news organization. And now that the monoclonal antibody treatments have been paused, convalescent plasma “is the only antibody-based therapy that is reliably available. Convalescent plasma includes thousands of different antibodies.”

With his colleagues, Dr. Casadevall evaluated plasma samples from 740 patients. Some had received booster vaccines and been infected with Omicron, others had received boosters and not been infected, and still others had not been vaccinated and became infected.

In a report (not yet peer-reviewed), they found the plasma from those who had been infected or boosted within the past 6 months neutralized the new Omicron variants BQ.1.1, XBB.1, and BF.7.
 

A push for boosters, masks

To get through the coming months, taking precautions like masking and distancing and staying up to date on booster vaccinations, especially for older adults, can make a difference, other experts say.

In a Twitter thread in early December, Peter Hotez, MD, PhD, professor of pediatrics and molecular virology and microbiology at Baylor College of Medicine, Houston, urged people to take COVID seriously as holiday parties and gatherings occur.

“The single most impactful thing you can do is get your bivalent booster,” he tweeted, as well as give your kids the booster, citing preliminary research that the bivalent mRNA booster broadens immunity against the Omicron subvariants.

For seniors, he said, ‘‘if you get breakthrough COVID, [it’s] really important to get Paxlovid.” Masks will help not only for COVID but also influenza, respiratory syncytial virus (RSV), and other conditions.

Mitigation measures have largely been abandoned, according to Eric Topol, MD, director of the Scripps Research Translational Institute, La Jolla, Calif., and editor-in-chief of Medscape. In an op-ed in the Los Angeles Times, and on his Twitter feed, he reminds people about masking and urges people to get the bivalent booster.

According to the Centers for Disease Control and Prevention, as of Dec. 8, only 13.5% of people aged 5 and older have gotten an updated booster, despite research that shows an increase in antibodies to BQ.1.1. Recent research has found that the bivalent booster increases antibodies to BQ.1.1 by up to 10-fold, Dr. Topol said.

Dr. Adalja is on advisory boards for Shionogi, GSK, and Pardes. Dr. Casadevall reports no relevant financial relationships.

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

It was the last monoclonal antibody treatment standing. But less than 10 months after the U.S. Food and Drug Administration gave bebtelovimab its emergency use authorization (EUA) to fight COVID-19, it earlier this month de-authorized it, just as it had for other monoclonal antibody treatments, and for the same reason: The treatments were outwitted by the viral mutations.
 

Bebtelovimab couldn’t neutralize the Omicron subvariants BQ.1 and BQ.1.1, the cause of nearly 60% of COVID cases nationally as of November 30.

Next on the chopping block, some predict, will be Evusheld, the combination of tixagevimab and cilgavimab given as a preventive monoclonal antibody to people who are immunocompromised and at high risk of contracting COVID and to those who can’t take the vaccine. In October, the FDA warned that Evusheld was not neutralizing circulating COVID variants.

As the options for treating and preventing COVID decline, will companies rally quickly to develop new ones, or cut their losses in developing treatments that may work for only a few months, given the speed of viral mutations?

But although monoclonal antibody treatments are off the table, at least for now, antiviral drugs – including Paxlovid – are still very much available, and some say underused.

Others suggest it’s time to resurrect interest in convalescent plasma, a treatment used early in the pandemic before drugs or vaccines were here and still authorized for use in those who are immunosuppressed or receiving immunosuppressive treatment.

And on the prevention front, staying up to date with booster vaccines, masking, and taking other precautions should be stressed more, others say, regardless of the number of treatment options, and especially now, as cases rise and people gather for the winter holidays.
 

‘A major setback’

The bebtelovimab de-authorization was “a major setback,” but an understandable one, said Arturo Casadevall, MD, PhD, professor and chair of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health in Baltimore. “Monoclonal antibodies are great drugs. We are in an unfortunate situation in that they are vulnerable to changes in the virus” and can’t offer long-lasting protection.

Supplies of bebtelovimab will be retained, according to the FDA, in case variants susceptible to it return.

“What happened to bebtelovimab is no surprise,” agreed Amesh Adalja, MD, senior scholar at Johns Hopkins Center for Health Security. “This is what is going to happen when you are targeting a virus that mutates a lot.”

Monoclonal antibodies work by binding to the spike protein on the virus surface to prevent it from entering cells.

However, Dr. Adalja doesn’t view the disappearance of monoclonal antibody treatments as a major setback. Monoclonal antibodies were not the primary way COVID was treated, he said.

While he does believe it’s important that more monoclonal antibody treatments be developed, “I think it’s important to remember we still have Paxlovid while everyone is lamenting the loss of bebtelovimab.’’
 

Antivirals: What’s here, what’s coming

Compared with monoclonal antibodies, “Paxlovid remains a much easier drug to give,” Dr. Adalja told this news organization, because it is taken orally, not intravenously.

And it’s effective. In a recent study, researchers found that adults diagnosed with COVID given Paxlovid within 5 days of diagnosis had a 51% lower hospitalization rate within the next 30 days than those not given it. Another study shows it could also reduce a person’s risk of developing long COVID by 26%.

Paxlovid is underused, Dr. Adalja said, partly because the rebound potential got more press than the effectiveness. When a celebrity got rebound from Paxlovid, he said, that would make the news, overshadowing the research on its effectiveness.

Besides Paxlovid, the antivirals remdesivir (Veklury), given intravenously for 3 days, and molnupiravir (Lagevrio), taken orally, are also still available. Antivirals work by targeting specific parts of the virus to prevent it from multiplying.

In the lab, remdesivir, molnupiravir, and another antiviral, nirmatrelvir, all appear to be effective against both BQ.1.1 (a BA.5 subvariant) and XBB (a BA.2 subvariant), both rapidly rising in the United States, according to a report last week in the New England Journal of Medicine.

The researchers also tested several monoclonal antibodies and found they did not neutralize either of the subvariants BQ.1.1 and XBB.

A new oral antiviral, Xocova (ensitrelvir fumaric acid), from Japanese manufacturer Shionogi, received emergency approval in Japan on November 22. It’s taken once a day for 5 days. The goal is to expand access to it globally, according to the company.

Pardes Biosciences launched a phase 2 trial in September for its oral antiviral drug (PBI-0451), under study as a treatment and preventive for COVID. It expects data by the first quarter of 2023.

Pfizer, which makes Paxlovid, has partnered with Clear Creek Bio to develop another oral antiviral COVID drug.
 

Other approaches

A receptor protein known as ACE2 (angiotensin-converting enzyme 2) is the main “doorway” that SARS-CoV-2 uses to enter and infect cells.

Dana-Farber Cancer Institute scientists are developing a “decoy” drug that works by mimicking the ACE2 receptor on the surface of cells; when the virus tries to bind to it, the spike protein is destroyed. Human trials have not yet started.

Other researchers are investigating whether an already-approved drug used to treat a liver disease, Actigall (UDCA/ursodeoxycholic acid), could protect against COVID infection by reducing ACE2.

So far, the researchers have found in early research that people taking UDCA for liver conditions were less likely than those not taking the drug to have severe COVID. They also found that UDCA reduced SARS-CoV-2 infection in human lungs maintained outside the body.
 

Monoclonal antibody treatments?

After the FDA decision to withdraw the bebtelovimab EUA, which Eli Lilly said it agreed with, the company issued a statement, promising it wasn’t giving up on monoclonal antibody treatments.

“Lilly will continue to search and evaluate monoclonal antibodies to identify potential candidates for clinical development against new variants,” it read in part.

AstraZeneca, which makes Evusheld, is also continuing to work on monoclonal antibody development. According to a spokesperson, “We are also developing a new long-acting antibody combination – AZD5156 – which has been shown in the lab to neutralize emerging new variants and all known variants to date. We are working to accelerate the development of AZD5156 to make it available at the end of 2023.”

The AstraZeneca spokesperson said he could share no more information about what the combination would include.
 

A convalescent plasma comeback?

Although Paxlovid can help, there are many contraindications to it, such as drug-drug interactions, Dr. Casadevall told this news organization. And now that the monoclonal antibody treatments have been paused, convalescent plasma “is the only antibody-based therapy that is reliably available. Convalescent plasma includes thousands of different antibodies.”

With his colleagues, Dr. Casadevall evaluated plasma samples from 740 patients. Some had received booster vaccines and been infected with Omicron, others had received boosters and not been infected, and still others had not been vaccinated and became infected.

In a report (not yet peer-reviewed), they found the plasma from those who had been infected or boosted within the past 6 months neutralized the new Omicron variants BQ.1.1, XBB.1, and BF.7.
 

A push for boosters, masks

To get through the coming months, taking precautions like masking and distancing and staying up to date on booster vaccinations, especially for older adults, can make a difference, other experts say.

In a Twitter thread in early December, Peter Hotez, MD, PhD, professor of pediatrics and molecular virology and microbiology at Baylor College of Medicine, Houston, urged people to take COVID seriously as holiday parties and gatherings occur.

“The single most impactful thing you can do is get your bivalent booster,” he tweeted, as well as give your kids the booster, citing preliminary research that the bivalent mRNA booster broadens immunity against the Omicron subvariants.

For seniors, he said, ‘‘if you get breakthrough COVID, [it’s] really important to get Paxlovid.” Masks will help not only for COVID but also influenza, respiratory syncytial virus (RSV), and other conditions.

Mitigation measures have largely been abandoned, according to Eric Topol, MD, director of the Scripps Research Translational Institute, La Jolla, Calif., and editor-in-chief of Medscape. In an op-ed in the Los Angeles Times, and on his Twitter feed, he reminds people about masking and urges people to get the bivalent booster.

According to the Centers for Disease Control and Prevention, as of Dec. 8, only 13.5% of people aged 5 and older have gotten an updated booster, despite research that shows an increase in antibodies to BQ.1.1. Recent research has found that the bivalent booster increases antibodies to BQ.1.1 by up to 10-fold, Dr. Topol said.

Dr. Adalja is on advisory boards for Shionogi, GSK, and Pardes. Dr. Casadevall reports no relevant financial relationships.

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

First described in 2020 by researchers from the U.S. National Institutes of Health, VEXAS syndrome is a systemic autoinflammatory disease of undefined origin. Its name is an acronym: Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic. The prevalence of this syndrome is unknown, but it is not so rare. As it is an X-linked disease, men are predominantly affected.

First identification

The NIH team screened the exomes and genomes of 2,560 individuals. Of this group, 1,477 had been referred because of undiagnosed recurrent fevers, systemic inflammation, or both, and 1,083 were affected by atypical, unclassified disorders. The researchers identified 25 men with a somatic mutation in the ubiquitin-like modifier activating enzyme 1 (UBA1) gene, which is involved in the protein ubiquitylation system. This posttranslational modification has a pleiotropic function that likely explains the clinical heterogeneity seen in VEXAS patients: regulation of protein turnover, especially those involved in the cell cycle, cell death, and signal transduction. Ubiquitylation is also involved in nonproteolytic functions, such as assembly of multiprotein complexes, intracellular signaling, inflammatory signaling, and DNA repair.

Clinical presentation

The clinicobiological presentation of VEXAS syndrome is very heterogeneous. Typically, patients present with a systemic inflammatory disease with unexplained episodes of fever, involvement of the lungs, skin, blood vessels, and joints. Molecular diagnosis is made by the sequencing of UBA1.

Most patients present with the characteristic clinical signs of other inflammatory diseases, such as polyarteritis nodosa and recurrent polychondritis. But VEXAS patients are at high risk of developing hematologic conditions. Indeed, the following were seen among the 25 participants in the NIH study: macrocytic anemia (96%), venous thromboembolism (44%), myelodysplastic syndrome (24%), and multiple myeloma or monoclonal gammopathy of undetermined significance (20%).

In VEXAS patients, levels of serum inflammatory markers are increased. These markers include tumor necrosis factor, interleukin-8, interleukin-6, interferon-inducible protein-10, interferon-gamma, C-reactive protein. In addition, there is aberrant activation of innate immune-signaling pathways.

In a large-scale analysis of a multicenter case series of 116 French patients, researchers found that VEXAS syndrome primarily affected men. The disease was progressive, and onset occurred after age 50 years. These patients can be divided into three phenotypically distinct clusters on the basis of integration of clinical and biological data. In the 58 cases in which myelodysplastic syndrome was present, the mortality rates were higher. The researchers also reported that the UBA1 p.Met41L mutation was associated with a better prognosis.
 

Treatment data

VEXAS syndrome resists the classical therapeutic arsenal. Patients require high-dose glucocorticoids, and prognosis appears to be poor. The available treatment data are retrospective. Of the 25 participants in the NIH study, 40% died within 5 years from disease-related causes or complications related to treatment. Among the promising therapeutic avenues is the use of inhibitors of the Janus kinase pathway.

This article was translated from Univadis France. A version of this article appeared on Medscape.com.

First described in 2020 by researchers from the U.S. National Institutes of Health, VEXAS syndrome is a systemic autoinflammatory disease of undefined origin. Its name is an acronym: Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic. The prevalence of this syndrome is unknown, but it is not so rare. As it is an X-linked disease, men are predominantly affected.

First identification

The NIH team screened the exomes and genomes of 2,560 individuals. Of this group, 1,477 had been referred because of undiagnosed recurrent fevers, systemic inflammation, or both, and 1,083 were affected by atypical, unclassified disorders. The researchers identified 25 men with a somatic mutation in the ubiquitin-like modifier activating enzyme 1 (UBA1) gene, which is involved in the protein ubiquitylation system. This posttranslational modification has a pleiotropic function that likely explains the clinical heterogeneity seen in VEXAS patients: regulation of protein turnover, especially those involved in the cell cycle, cell death, and signal transduction. Ubiquitylation is also involved in nonproteolytic functions, such as assembly of multiprotein complexes, intracellular signaling, inflammatory signaling, and DNA repair.

Clinical presentation

The clinicobiological presentation of VEXAS syndrome is very heterogeneous. Typically, patients present with a systemic inflammatory disease with unexplained episodes of fever, involvement of the lungs, skin, blood vessels, and joints. Molecular diagnosis is made by the sequencing of UBA1.

Most patients present with the characteristic clinical signs of other inflammatory diseases, such as polyarteritis nodosa and recurrent polychondritis. But VEXAS patients are at high risk of developing hematologic conditions. Indeed, the following were seen among the 25 participants in the NIH study: macrocytic anemia (96%), venous thromboembolism (44%), myelodysplastic syndrome (24%), and multiple myeloma or monoclonal gammopathy of undetermined significance (20%).

In VEXAS patients, levels of serum inflammatory markers are increased. These markers include tumor necrosis factor, interleukin-8, interleukin-6, interferon-inducible protein-10, interferon-gamma, C-reactive protein. In addition, there is aberrant activation of innate immune-signaling pathways.

In a large-scale analysis of a multicenter case series of 116 French patients, researchers found that VEXAS syndrome primarily affected men. The disease was progressive, and onset occurred after age 50 years. These patients can be divided into three phenotypically distinct clusters on the basis of integration of clinical and biological data. In the 58 cases in which myelodysplastic syndrome was present, the mortality rates were higher. The researchers also reported that the UBA1 p.Met41L mutation was associated with a better prognosis.
 

Treatment data

VEXAS syndrome resists the classical therapeutic arsenal. Patients require high-dose glucocorticoids, and prognosis appears to be poor. The available treatment data are retrospective. Of the 25 participants in the NIH study, 40% died within 5 years from disease-related causes or complications related to treatment. Among the promising therapeutic avenues is the use of inhibitors of the Janus kinase pathway.

This article was translated from Univadis France. A version of this article appeared on Medscape.com.

First described in 2020 by researchers from the U.S. National Institutes of Health, VEXAS syndrome is a systemic autoinflammatory disease of undefined origin. Its name is an acronym: Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic. The prevalence of this syndrome is unknown, but it is not so rare. As it is an X-linked disease, men are predominantly affected.

First identification

The NIH team screened the exomes and genomes of 2,560 individuals. Of this group, 1,477 had been referred because of undiagnosed recurrent fevers, systemic inflammation, or both, and 1,083 were affected by atypical, unclassified disorders. The researchers identified 25 men with a somatic mutation in the ubiquitin-like modifier activating enzyme 1 (UBA1) gene, which is involved in the protein ubiquitylation system. This posttranslational modification has a pleiotropic function that likely explains the clinical heterogeneity seen in VEXAS patients: regulation of protein turnover, especially those involved in the cell cycle, cell death, and signal transduction. Ubiquitylation is also involved in nonproteolytic functions, such as assembly of multiprotein complexes, intracellular signaling, inflammatory signaling, and DNA repair.

Clinical presentation

The clinicobiological presentation of VEXAS syndrome is very heterogeneous. Typically, patients present with a systemic inflammatory disease with unexplained episodes of fever, involvement of the lungs, skin, blood vessels, and joints. Molecular diagnosis is made by the sequencing of UBA1.

Most patients present with the characteristic clinical signs of other inflammatory diseases, such as polyarteritis nodosa and recurrent polychondritis. But VEXAS patients are at high risk of developing hematologic conditions. Indeed, the following were seen among the 25 participants in the NIH study: macrocytic anemia (96%), venous thromboembolism (44%), myelodysplastic syndrome (24%), and multiple myeloma or monoclonal gammopathy of undetermined significance (20%).

In VEXAS patients, levels of serum inflammatory markers are increased. These markers include tumor necrosis factor, interleukin-8, interleukin-6, interferon-inducible protein-10, interferon-gamma, C-reactive protein. In addition, there is aberrant activation of innate immune-signaling pathways.

In a large-scale analysis of a multicenter case series of 116 French patients, researchers found that VEXAS syndrome primarily affected men. The disease was progressive, and onset occurred after age 50 years. These patients can be divided into three phenotypically distinct clusters on the basis of integration of clinical and biological data. In the 58 cases in which myelodysplastic syndrome was present, the mortality rates were higher. The researchers also reported that the UBA1 p.Met41L mutation was associated with a better prognosis.
 

Treatment data

VEXAS syndrome resists the classical therapeutic arsenal. Patients require high-dose glucocorticoids, and prognosis appears to be poor. The available treatment data are retrospective. Of the 25 participants in the NIH study, 40% died within 5 years from disease-related causes or complications related to treatment. Among the promising therapeutic avenues is the use of inhibitors of the Janus kinase pathway.

This article was translated from Univadis France. A version of this article appeared on Medscape.com.

Jackie Dishner hasn’t been the same since June 2020, when COVID-19 robbed her of her energy level, ability to think clearly, and sense of taste and smell. Yet at 58, the Arizona writer is in no hurry to get the latest vaccine booster. “I just don’t want to risk getting any sicker,” she said.

Ms. Dishner has had two doses of vaccine plus two boosters. Each time, she had what regulators consider to be mild reactions, including a sore arm, slight fever, nausea, and body aches. Still, there’s some evidence that the newest booster, which protects against some of the later variants, could help people like Ms. Dishner in several ways, said Ziyad Al-Aly, MD, a clinical epidemiologist and prolific long COVID researcher at Washington University in St. Louis.

“A bivalent booster might actually [help with] your long COVID,” he said.

There may be other benefits. “What vaccines or current vaccine boosters do is reduce your risk of progression to severe COVID-19 illness,” Dr. Al-Aly said. “You are avoiding hospital stays or even worse; you’re avoiding potentially fatal outcomes after infection. And that’s really worth it. Who wants to be in the hospital this Christmas holiday?”

Each time people are infected with SARS-CoV-2, the virus that causes COVID-19, they have a fresh risk of not only getting severely ill or dying, but of developing long COVID, Dr. Al-Aly and colleagues found in a study published in Nature Medicine. “If you dodged the bullet the first time and did not get long COVID after the first infection, if you get reinfected, you’re trying your luck again,” Dr. Al-Aly said. “I would advise people not to get reinfected, which is another reason to get the booster.” 

In a recent review in The Lancet eClinicalMedicine, an international team of researchers looked at 11 studies that sought to find out if vaccines affected long COVID symptoms. Seven of those studies found that people’s symptoms improved after they were vaccinated, and four found that symptoms mostly remained the same. One found symptoms got worse in some patients. 

A study of 28,000 people published in the British Medical Journal found more evidence that vaccination may help ease symptoms. “Vaccination may contribute to a reduction in the population health burden of long COVID,” the team at the United Kingdom’s Office for National Statistics concluded. Most studies found vaccination reduced the risk of getting long COVID in the first place.

Vaccines prompt the body to produce antibodies, which stop a microbe from infecting cells. They also prompt the production of immune cells called T cells, which continue to hunt down and attack a pathogen even after infection.

A booster dose could help rev up that immune response in a patient with long COVID, said Stephen J. Thomas, MD, an infectious disease specialist at Upstate Medical Center in Syracuse, N.Y., and the center’s lead principal investigator for Pfizer/BioNTech’s COVID-19 2020 vaccine trial.

Some scientists believe long COVID might be caused when the virus persists in parts of the body where the immune system isn’t particularly active. Although they don’t fully understand the workings of the many and varied long COVID symptoms, they have a good idea about why people with long COVID often do better after receiving a vaccine or booster.

“The theory is that by boosting, the immune system may be able to ‘mop up’ those virus stragglers that have remained behind after your first cleanup attempt,” Dr. Thomas said.

“The vaccine is almost lending a hand or helping your immune response to clear that virus,” Dr. Al-Aly said.

It could be difficult for long COVID patients to make an informed decision about boosters, given the lack of studies that focus exclusively on the relationship between long COVID and boosters, according to Scott Roberts, MD, associate medical director for infection prevention at Yale New Haven (Conn.) Hospital. 

Dr. Roberts recommended that patients speak with their health care providers and read about the bivalent booster on trusted sites such as those sponsored by the Food and Drug Administration and the Centers for Disease Control and Prevention. Long COVID patients should get the latest boosters, especially as there’s no evidence they are unsafe for them. “The antibody response is appropriately boosted, and there is a decent chance this will help reduce the impact of long COVID as well,” he said. “Waiting will only increase the risk of getting infected and increase the chances of long COVID.”

Only 12% of Americans 5 years and older have received the updated booster, according to the CDC, although it’s recommended for everyone. Just over 80% of Americans have gotten at least one vaccine dose. Dr. Thomas understands why the uptake has been so low: Along with people like Ms. Dishner, who fear more side effects or worse symptoms, there are those who believe that hybrid immunity – vaccination immunity plus natural infection – is superior to vaccination alone and that they don’t need a booster.

Studies show that the bivalent boosters, which protect against older and newer variants, can target even the new, predominant COVID-19 strains. Whether that is enough to convince people in the no-booster camp who lost faith when their vaccinated peers started getting COVID-19 is unclear, although, as Dr. Al-Aly has pointed out, vaccinations help keep people from getting so sick that they wind up in the hospital. And, with most of the population having received at least one dose of vaccine, most of those getting infected will naturally come from among the vaccinated.

Thomas describes the expectation that vaccines would prevent everyone from getting sick as “one of the major fails” of the pandemic.

Counting on a vaccine to confer 100% immunity is “a very high bar,” he said. “I think that’s what people expected, and when they weren’t seeing it, they kind of said: ‘Well, what’s the point? You know, things are getting better. I’d rather take my chances than keep going and getting boosted.’ ”

One point – and it’s a critical one – is that vaccination immunity wanes. Plus new variants arise that can evade at least some of the immunity provided by vaccination. That’s why boosters are built into the COVID vaccination program.

While it’s not clear why some long COVID patients see improvements in their symptoms after being vaccinated or boosted and others do not, Dr. Al-Aly said there’s little evidence vaccines can make long COVID worse. “There are some reports out there that some people with long COVID, when they got a vaccine or booster, their symptoms got worse. You’ll read anecdotes on this side,” he said, adding that efforts to see if this is really happening have been inconclusive.

“The general consensus is that vaccines really save lives,” Dr. Al-Aly said. “Getting vaccinated, even if you are a long COVID patient, is better than not getting vaccinated.”

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

Jackie Dishner hasn’t been the same since June 2020, when COVID-19 robbed her of her energy level, ability to think clearly, and sense of taste and smell. Yet at 58, the Arizona writer is in no hurry to get the latest vaccine booster. “I just don’t want to risk getting any sicker,” she said.

Ms. Dishner has had two doses of vaccine plus two boosters. Each time, she had what regulators consider to be mild reactions, including a sore arm, slight fever, nausea, and body aches. Still, there’s some evidence that the newest booster, which protects against some of the later variants, could help people like Ms. Dishner in several ways, said Ziyad Al-Aly, MD, a clinical epidemiologist and prolific long COVID researcher at Washington University in St. Louis.

“A bivalent booster might actually [help with] your long COVID,” he said.

There may be other benefits. “What vaccines or current vaccine boosters do is reduce your risk of progression to severe COVID-19 illness,” Dr. Al-Aly said. “You are avoiding hospital stays or even worse; you’re avoiding potentially fatal outcomes after infection. And that’s really worth it. Who wants to be in the hospital this Christmas holiday?”

Each time people are infected with SARS-CoV-2, the virus that causes COVID-19, they have a fresh risk of not only getting severely ill or dying, but of developing long COVID, Dr. Al-Aly and colleagues found in a study published in Nature Medicine. “If you dodged the bullet the first time and did not get long COVID after the first infection, if you get reinfected, you’re trying your luck again,” Dr. Al-Aly said. “I would advise people not to get reinfected, which is another reason to get the booster.” 

In a recent review in The Lancet eClinicalMedicine, an international team of researchers looked at 11 studies that sought to find out if vaccines affected long COVID symptoms. Seven of those studies found that people’s symptoms improved after they were vaccinated, and four found that symptoms mostly remained the same. One found symptoms got worse in some patients. 

A study of 28,000 people published in the British Medical Journal found more evidence that vaccination may help ease symptoms. “Vaccination may contribute to a reduction in the population health burden of long COVID,” the team at the United Kingdom’s Office for National Statistics concluded. Most studies found vaccination reduced the risk of getting long COVID in the first place.

Vaccines prompt the body to produce antibodies, which stop a microbe from infecting cells. They also prompt the production of immune cells called T cells, which continue to hunt down and attack a pathogen even after infection.

A booster dose could help rev up that immune response in a patient with long COVID, said Stephen J. Thomas, MD, an infectious disease specialist at Upstate Medical Center in Syracuse, N.Y., and the center’s lead principal investigator for Pfizer/BioNTech’s COVID-19 2020 vaccine trial.

Some scientists believe long COVID might be caused when the virus persists in parts of the body where the immune system isn’t particularly active. Although they don’t fully understand the workings of the many and varied long COVID symptoms, they have a good idea about why people with long COVID often do better after receiving a vaccine or booster.

“The theory is that by boosting, the immune system may be able to ‘mop up’ those virus stragglers that have remained behind after your first cleanup attempt,” Dr. Thomas said.

“The vaccine is almost lending a hand or helping your immune response to clear that virus,” Dr. Al-Aly said.

It could be difficult for long COVID patients to make an informed decision about boosters, given the lack of studies that focus exclusively on the relationship between long COVID and boosters, according to Scott Roberts, MD, associate medical director for infection prevention at Yale New Haven (Conn.) Hospital. 

Dr. Roberts recommended that patients speak with their health care providers and read about the bivalent booster on trusted sites such as those sponsored by the Food and Drug Administration and the Centers for Disease Control and Prevention. Long COVID patients should get the latest boosters, especially as there’s no evidence they are unsafe for them. “The antibody response is appropriately boosted, and there is a decent chance this will help reduce the impact of long COVID as well,” he said. “Waiting will only increase the risk of getting infected and increase the chances of long COVID.”

Only 12% of Americans 5 years and older have received the updated booster, according to the CDC, although it’s recommended for everyone. Just over 80% of Americans have gotten at least one vaccine dose. Dr. Thomas understands why the uptake has been so low: Along with people like Ms. Dishner, who fear more side effects or worse symptoms, there are those who believe that hybrid immunity – vaccination immunity plus natural infection – is superior to vaccination alone and that they don’t need a booster.

Studies show that the bivalent boosters, which protect against older and newer variants, can target even the new, predominant COVID-19 strains. Whether that is enough to convince people in the no-booster camp who lost faith when their vaccinated peers started getting COVID-19 is unclear, although, as Dr. Al-Aly has pointed out, vaccinations help keep people from getting so sick that they wind up in the hospital. And, with most of the population having received at least one dose of vaccine, most of those getting infected will naturally come from among the vaccinated.

Thomas describes the expectation that vaccines would prevent everyone from getting sick as “one of the major fails” of the pandemic.

Counting on a vaccine to confer 100% immunity is “a very high bar,” he said. “I think that’s what people expected, and when they weren’t seeing it, they kind of said: ‘Well, what’s the point? You know, things are getting better. I’d rather take my chances than keep going and getting boosted.’ ”

One point – and it’s a critical one – is that vaccination immunity wanes. Plus new variants arise that can evade at least some of the immunity provided by vaccination. That’s why boosters are built into the COVID vaccination program.

While it’s not clear why some long COVID patients see improvements in their symptoms after being vaccinated or boosted and others do not, Dr. Al-Aly said there’s little evidence vaccines can make long COVID worse. “There are some reports out there that some people with long COVID, when they got a vaccine or booster, their symptoms got worse. You’ll read anecdotes on this side,” he said, adding that efforts to see if this is really happening have been inconclusive.

“The general consensus is that vaccines really save lives,” Dr. Al-Aly said. “Getting vaccinated, even if you are a long COVID patient, is better than not getting vaccinated.”

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

Jackie Dishner hasn’t been the same since June 2020, when COVID-19 robbed her of her energy level, ability to think clearly, and sense of taste and smell. Yet at 58, the Arizona writer is in no hurry to get the latest vaccine booster. “I just don’t want to risk getting any sicker,” she said.

Ms. Dishner has had two doses of vaccine plus two boosters. Each time, she had what regulators consider to be mild reactions, including a sore arm, slight fever, nausea, and body aches. Still, there’s some evidence that the newest booster, which protects against some of the later variants, could help people like Ms. Dishner in several ways, said Ziyad Al-Aly, MD, a clinical epidemiologist and prolific long COVID researcher at Washington University in St. Louis.

“A bivalent booster might actually [help with] your long COVID,” he said.

There may be other benefits. “What vaccines or current vaccine boosters do is reduce your risk of progression to severe COVID-19 illness,” Dr. Al-Aly said. “You are avoiding hospital stays or even worse; you’re avoiding potentially fatal outcomes after infection. And that’s really worth it. Who wants to be in the hospital this Christmas holiday?”

Each time people are infected with SARS-CoV-2, the virus that causes COVID-19, they have a fresh risk of not only getting severely ill or dying, but of developing long COVID, Dr. Al-Aly and colleagues found in a study published in Nature Medicine. “If you dodged the bullet the first time and did not get long COVID after the first infection, if you get reinfected, you’re trying your luck again,” Dr. Al-Aly said. “I would advise people not to get reinfected, which is another reason to get the booster.” 

In a recent review in The Lancet eClinicalMedicine, an international team of researchers looked at 11 studies that sought to find out if vaccines affected long COVID symptoms. Seven of those studies found that people’s symptoms improved after they were vaccinated, and four found that symptoms mostly remained the same. One found symptoms got worse in some patients. 

A study of 28,000 people published in the British Medical Journal found more evidence that vaccination may help ease symptoms. “Vaccination may contribute to a reduction in the population health burden of long COVID,” the team at the United Kingdom’s Office for National Statistics concluded. Most studies found vaccination reduced the risk of getting long COVID in the first place.

Vaccines prompt the body to produce antibodies, which stop a microbe from infecting cells. They also prompt the production of immune cells called T cells, which continue to hunt down and attack a pathogen even after infection.

A booster dose could help rev up that immune response in a patient with long COVID, said Stephen J. Thomas, MD, an infectious disease specialist at Upstate Medical Center in Syracuse, N.Y., and the center’s lead principal investigator for Pfizer/BioNTech’s COVID-19 2020 vaccine trial.

Some scientists believe long COVID might be caused when the virus persists in parts of the body where the immune system isn’t particularly active. Although they don’t fully understand the workings of the many and varied long COVID symptoms, they have a good idea about why people with long COVID often do better after receiving a vaccine or booster.

“The theory is that by boosting, the immune system may be able to ‘mop up’ those virus stragglers that have remained behind after your first cleanup attempt,” Dr. Thomas said.

“The vaccine is almost lending a hand or helping your immune response to clear that virus,” Dr. Al-Aly said.

It could be difficult for long COVID patients to make an informed decision about boosters, given the lack of studies that focus exclusively on the relationship between long COVID and boosters, according to Scott Roberts, MD, associate medical director for infection prevention at Yale New Haven (Conn.) Hospital. 

Dr. Roberts recommended that patients speak with their health care providers and read about the bivalent booster on trusted sites such as those sponsored by the Food and Drug Administration and the Centers for Disease Control and Prevention. Long COVID patients should get the latest boosters, especially as there’s no evidence they are unsafe for them. “The antibody response is appropriately boosted, and there is a decent chance this will help reduce the impact of long COVID as well,” he said. “Waiting will only increase the risk of getting infected and increase the chances of long COVID.”

Only 12% of Americans 5 years and older have received the updated booster, according to the CDC, although it’s recommended for everyone. Just over 80% of Americans have gotten at least one vaccine dose. Dr. Thomas understands why the uptake has been so low: Along with people like Ms. Dishner, who fear more side effects or worse symptoms, there are those who believe that hybrid immunity – vaccination immunity plus natural infection – is superior to vaccination alone and that they don’t need a booster.

Studies show that the bivalent boosters, which protect against older and newer variants, can target even the new, predominant COVID-19 strains. Whether that is enough to convince people in the no-booster camp who lost faith when their vaccinated peers started getting COVID-19 is unclear, although, as Dr. Al-Aly has pointed out, vaccinations help keep people from getting so sick that they wind up in the hospital. And, with most of the population having received at least one dose of vaccine, most of those getting infected will naturally come from among the vaccinated.

Thomas describes the expectation that vaccines would prevent everyone from getting sick as “one of the major fails” of the pandemic.

Counting on a vaccine to confer 100% immunity is “a very high bar,” he said. “I think that’s what people expected, and when they weren’t seeing it, they kind of said: ‘Well, what’s the point? You know, things are getting better. I’d rather take my chances than keep going and getting boosted.’ ”

One point – and it’s a critical one – is that vaccination immunity wanes. Plus new variants arise that can evade at least some of the immunity provided by vaccination. That’s why boosters are built into the COVID vaccination program.

While it’s not clear why some long COVID patients see improvements in their symptoms after being vaccinated or boosted and others do not, Dr. Al-Aly said there’s little evidence vaccines can make long COVID worse. “There are some reports out there that some people with long COVID, when they got a vaccine or booster, their symptoms got worse. You’ll read anecdotes on this side,” he said, adding that efforts to see if this is really happening have been inconclusive.

“The general consensus is that vaccines really save lives,” Dr. Al-Aly said. “Getting vaccinated, even if you are a long COVID patient, is better than not getting vaccinated.”

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