Journal of Clinical Outcomes Management

The White House declared monkeypox a public health emergency Aug. 4. There have been more than 6,600 reported cases of the disease in the United States, up from less than 5,000 cases reported last week.

“This public health emergency will allow us to explore additional strategies to get vaccines and treatments more quickly out in the affected communities. And it will allow us to get more data from jurisdictions so we can effectively track and attack this outbreak,” Robert Fenton, who was named as the national monkeypox response coordinator this week, said at a news briefing Aug. 4.

Those who catch the virus usually have fever-like symptoms, followed by red lesions on the body that can raise and develop pus. Those at highest risk of monkeypox are gay and bisexual men, as well as men who have sex with other men. There are between 1.6 million and 1.7 million Americans in this high-risk group, Health and Human Services Secretary Xavier Becerra said at the briefing.

The Jynneos vaccine is being distributed to protect against monkeypox and can prevent severe symptoms. It’s mostly going to those with the greatest risk of catching the virus.

Last week, the Biden administration made over 1.1 million doses of the Jynneos vaccine available – of which over 600,000 doses have already been distributed across the country – and have secured over 6.9 million Jynneos doses altogether.

Around 786,000 vaccines have already been allocated, and the first doses were shipped this week. States will be able to order more doses beginning Aug. 15. If a state has used 90% or more of its vaccine supply, it will be eligible to order more doses before Aug. 15, according to Dawn O’Connell, JD, assistant secretary for preparedness and response at the U.S. Department of Health and Human Services.

An additional 150,000 doses will be added to the national stockpile in September, with more doses to come later this year, Ms. O’Connell says.

The administration is also stressing the importance of monkeypox testing and says it can now distribute 80,000 monkeypox tests per week.

An antiviral drug – known as TPOXX – is also available to treat severe cases of monkeypox. Around 1,700,000 doses are available in the Strategic National Stockpile, public health officials say.

“We are prepared to take our response to the next level, and we urge every American to take this seriously and to take responsibility to help us tackle this virus,” Secretary Becerra told reporters.

The White House says it will continue reaching out to doctors, public health partners, LGBTQ advocates, and other impacted communities.

“The public health emergency further raises awareness about monkeypox, which will encourage clinicians to test for it,” Rochelle Walensky, MD, director of the Centers for Disease Control and Prevention, said at the briefing.

This week, President Joe Biden appointed a new White House monkeypox response team. Besides Mr. Fenton as the response coordinator, Demetre Daskalakis, MD, will serve as the White House national monkeypox response deputy coordinator. He is the director of the CDC’s Division of HIV Prevention.

“This virus is moving fast. This is a unique outbreak that is spreading faster than previous outbreaks,” Mr. Fenton told reporters Aug. 4. “That’s why the president asked me to explore everything we can do to combat monkeypox and protect communities at risk.”

This article was updated 8/4/22.

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

The White House declared monkeypox a public health emergency Aug. 4. There have been more than 6,600 reported cases of the disease in the United States, up from less than 5,000 cases reported last week.

“This public health emergency will allow us to explore additional strategies to get vaccines and treatments more quickly out in the affected communities. And it will allow us to get more data from jurisdictions so we can effectively track and attack this outbreak,” Robert Fenton, who was named as the national monkeypox response coordinator this week, said at a news briefing Aug. 4.

Those who catch the virus usually have fever-like symptoms, followed by red lesions on the body that can raise and develop pus. Those at highest risk of monkeypox are gay and bisexual men, as well as men who have sex with other men. There are between 1.6 million and 1.7 million Americans in this high-risk group, Health and Human Services Secretary Xavier Becerra said at the briefing.

The Jynneos vaccine is being distributed to protect against monkeypox and can prevent severe symptoms. It’s mostly going to those with the greatest risk of catching the virus.

Last week, the Biden administration made over 1.1 million doses of the Jynneos vaccine available – of which over 600,000 doses have already been distributed across the country – and have secured over 6.9 million Jynneos doses altogether.

Around 786,000 vaccines have already been allocated, and the first doses were shipped this week. States will be able to order more doses beginning Aug. 15. If a state has used 90% or more of its vaccine supply, it will be eligible to order more doses before Aug. 15, according to Dawn O’Connell, JD, assistant secretary for preparedness and response at the U.S. Department of Health and Human Services.

An additional 150,000 doses will be added to the national stockpile in September, with more doses to come later this year, Ms. O’Connell says.

The administration is also stressing the importance of monkeypox testing and says it can now distribute 80,000 monkeypox tests per week.

An antiviral drug – known as TPOXX – is also available to treat severe cases of monkeypox. Around 1,700,000 doses are available in the Strategic National Stockpile, public health officials say.

“We are prepared to take our response to the next level, and we urge every American to take this seriously and to take responsibility to help us tackle this virus,” Secretary Becerra told reporters.

The White House says it will continue reaching out to doctors, public health partners, LGBTQ advocates, and other impacted communities.

“The public health emergency further raises awareness about monkeypox, which will encourage clinicians to test for it,” Rochelle Walensky, MD, director of the Centers for Disease Control and Prevention, said at the briefing.

This week, President Joe Biden appointed a new White House monkeypox response team. Besides Mr. Fenton as the response coordinator, Demetre Daskalakis, MD, will serve as the White House national monkeypox response deputy coordinator. He is the director of the CDC’s Division of HIV Prevention.

“This virus is moving fast. This is a unique outbreak that is spreading faster than previous outbreaks,” Mr. Fenton told reporters Aug. 4. “That’s why the president asked me to explore everything we can do to combat monkeypox and protect communities at risk.”

This article was updated 8/4/22.

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

The White House declared monkeypox a public health emergency Aug. 4. There have been more than 6,600 reported cases of the disease in the United States, up from less than 5,000 cases reported last week.

“This public health emergency will allow us to explore additional strategies to get vaccines and treatments more quickly out in the affected communities. And it will allow us to get more data from jurisdictions so we can effectively track and attack this outbreak,” Robert Fenton, who was named as the national monkeypox response coordinator this week, said at a news briefing Aug. 4.

Those who catch the virus usually have fever-like symptoms, followed by red lesions on the body that can raise and develop pus. Those at highest risk of monkeypox are gay and bisexual men, as well as men who have sex with other men. There are between 1.6 million and 1.7 million Americans in this high-risk group, Health and Human Services Secretary Xavier Becerra said at the briefing.

The Jynneos vaccine is being distributed to protect against monkeypox and can prevent severe symptoms. It’s mostly going to those with the greatest risk of catching the virus.

Last week, the Biden administration made over 1.1 million doses of the Jynneos vaccine available – of which over 600,000 doses have already been distributed across the country – and have secured over 6.9 million Jynneos doses altogether.

Around 786,000 vaccines have already been allocated, and the first doses were shipped this week. States will be able to order more doses beginning Aug. 15. If a state has used 90% or more of its vaccine supply, it will be eligible to order more doses before Aug. 15, according to Dawn O’Connell, JD, assistant secretary for preparedness and response at the U.S. Department of Health and Human Services.

An additional 150,000 doses will be added to the national stockpile in September, with more doses to come later this year, Ms. O’Connell says.

The administration is also stressing the importance of monkeypox testing and says it can now distribute 80,000 monkeypox tests per week.

An antiviral drug – known as TPOXX – is also available to treat severe cases of monkeypox. Around 1,700,000 doses are available in the Strategic National Stockpile, public health officials say.

“We are prepared to take our response to the next level, and we urge every American to take this seriously and to take responsibility to help us tackle this virus,” Secretary Becerra told reporters.

The White House says it will continue reaching out to doctors, public health partners, LGBTQ advocates, and other impacted communities.

“The public health emergency further raises awareness about monkeypox, which will encourage clinicians to test for it,” Rochelle Walensky, MD, director of the Centers for Disease Control and Prevention, said at the briefing.

This week, President Joe Biden appointed a new White House monkeypox response team. Besides Mr. Fenton as the response coordinator, Demetre Daskalakis, MD, will serve as the White House national monkeypox response deputy coordinator. He is the director of the CDC’s Division of HIV Prevention.

“This virus is moving fast. This is a unique outbreak that is spreading faster than previous outbreaks,” Mr. Fenton told reporters Aug. 4. “That’s why the president asked me to explore everything we can do to combat monkeypox and protect communities at risk.”

This article was updated 8/4/22.

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

A new analysis projects steep increases by 2060 in the prevalence of cardiovascular (CV) risk factors and disease that will disproportionately affect non-White populations who have limited access to health care.

The study by Reza Mohebi, MD, Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues was published in the Journal of the American College of Cardiology.

“Even though several assumptions underlie these projections, the importance of this work cannot be overestimated,” Andreas P. Kalogeropoulos, MD, MPH, PhD, and Javed Butler, MD, MPH, MBA, wrote in an accompanying editorial. “The absolute numbers are staggering.”

From 2025 to 2060, the number of people with any one of four CV risk factors – type 2 diabetes, hypertension, dyslipidemia, and obesity – is projected to increase by 15.4 million, to 34.7 million.

And the number of people with of any one of four CV disease types – ischemic heart disease, heart failure, MI, and stroke – is projected to increase by 3.2 million, to 6.8 million.

Although the model predicts that the prevalence of CV risk factors will gradually decrease among White Americans, the highest prevalence of CV risk factors will be among the White population because of its overall size.

Conversely, the projected prevalence of CV risk factors is expected to increase in Black, Hispanic, Asian, and other race/ethnicity populations.

In parallel, the prevalence of CV disease is projected to decrease in the White population and increase among all other race/ethnicities, particularly in the Black and Hispanic populations.

Courtesy Massachusetts General Hospital

“Our results project a worrisome increase with a particularly ominous increase in risk factors and disease in our most vulnerable patients, including Blacks and Hispanics,” senior author James L. Januzzi Jr., MD, summarized in a video issued by the society.

“The steep rise in CV risk factors and disease reflects the generally higher prevalence in populations projected to increase in the United States, owing to immigration and growth, including Black or Hispanic individuals,” Dr. Januzzi, also from Massachusetts General and Harvard, said in an interview.

“The disproportionate size of the risk is expected in a sense, as minority populations are disproportionately disadvantaged with respect to their health care,” he said. “But whether it is expected or not, the increase in projected prevalence is, nonetheless, concerning and a call to action.”

This study identifies “areas of opportunity for change in the U.S. health care system,” he continued. “Business as usual will result in us encountering a huge number of individuals with CV risk factors and diseases.”

The results from the current analysis assume there will be no modification in health care policies or changes in access to care for at-risk populations, Dr. Mohebi and colleagues noted.

To “stem the rising tide of CV disease in at-risk individuals,” would require strategies such as “emphasis on education regarding CV risk factors, improving access to quality healthcare, and facilitating lower-cost access to effective therapies for treatment of CV risk factors,” according to the researchers.

“Such advances need to be applied in a more equitable way throughout the United States, however,” they cautioned.
 

Census plus NHANES data

The researchers used 2020 U.S. census data and projected growth and 2013-2018 U.S. National Health and Nutrition Survey data to estimate the number of people with CV risk factors and CV disease from 2025 to 2060.

The estimates are based on a growing population and a fixed frequency.

Changing demographic landscape

It is “striking” that the numbers of non-White individuals with CV risk factors is projected to surpass the number of White individuals over time, and the number of non-White individuals with CV disease will be almost as many as White individuals by the year 2060, the editorialists noted.

“From a policy perspective, this means that unless appropriate, targeted action is taken, disparities in the burden of cardiovascular disease are only going to be exacerbated over time,” wrote Dr. Kalogeropoulos, from Stony Brook (N.Y.) University, and Dr. Butler, from Baylor College of Medicine, Dallas.

“On the positive side,” they continued, “the absolute increase in the percent prevalence of cardiovascular risk factors and conditions is projected to lie within a manageable range,” assuming that specific prevention policies are implemented.

“This is an opportunity for professional societies, including the cardiovascular care community, to re-evaluate priorities and strategies, for both training and practice, to best match the growing demands of a changing demographic landscape in the United States,” Dr. Kalogeropoulos and Dr. Butler concluded.

Dr. Mohebi is supported by the Barry Fellowship. Dr. Januzzi is supported by the Hutter Family Professorship; is a Trustee of the American College of Cardiology; is a board member of Imbria Pharmaceuticals; has received grant support from Abbott Diagnostics, Applied Therapeutics, Innolife, and Novartis; has received consulting income from Abbott Diagnostics, Boehringer Ingelheim, Janssen, Novartis, and Roche Diagnostics; and participates in clinical endpoint committees/data safety monitoring boards for AbbVie, Siemens, Takeda, and Vifor. Dr. Kalogeropoulos has received research funding from the National Heart, Lung, and Blood Institute; the American Heart Association; and the Centers for Disease Control and Prevention. Dr. Butler has been a consultant for numerous pharmaceutical companies.

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

A new analysis projects steep increases by 2060 in the prevalence of cardiovascular (CV) risk factors and disease that will disproportionately affect non-White populations who have limited access to health care.

The study by Reza Mohebi, MD, Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues was published in the Journal of the American College of Cardiology.

“Even though several assumptions underlie these projections, the importance of this work cannot be overestimated,” Andreas P. Kalogeropoulos, MD, MPH, PhD, and Javed Butler, MD, MPH, MBA, wrote in an accompanying editorial. “The absolute numbers are staggering.”

From 2025 to 2060, the number of people with any one of four CV risk factors – type 2 diabetes, hypertension, dyslipidemia, and obesity – is projected to increase by 15.4 million, to 34.7 million.

And the number of people with of any one of four CV disease types – ischemic heart disease, heart failure, MI, and stroke – is projected to increase by 3.2 million, to 6.8 million.

Although the model predicts that the prevalence of CV risk factors will gradually decrease among White Americans, the highest prevalence of CV risk factors will be among the White population because of its overall size.

Conversely, the projected prevalence of CV risk factors is expected to increase in Black, Hispanic, Asian, and other race/ethnicity populations.

In parallel, the prevalence of CV disease is projected to decrease in the White population and increase among all other race/ethnicities, particularly in the Black and Hispanic populations.

Courtesy Massachusetts General Hospital

“Our results project a worrisome increase with a particularly ominous increase in risk factors and disease in our most vulnerable patients, including Blacks and Hispanics,” senior author James L. Januzzi Jr., MD, summarized in a video issued by the society.

“The steep rise in CV risk factors and disease reflects the generally higher prevalence in populations projected to increase in the United States, owing to immigration and growth, including Black or Hispanic individuals,” Dr. Januzzi, also from Massachusetts General and Harvard, said in an interview.

“The disproportionate size of the risk is expected in a sense, as minority populations are disproportionately disadvantaged with respect to their health care,” he said. “But whether it is expected or not, the increase in projected prevalence is, nonetheless, concerning and a call to action.”

This study identifies “areas of opportunity for change in the U.S. health care system,” he continued. “Business as usual will result in us encountering a huge number of individuals with CV risk factors and diseases.”

The results from the current analysis assume there will be no modification in health care policies or changes in access to care for at-risk populations, Dr. Mohebi and colleagues noted.

To “stem the rising tide of CV disease in at-risk individuals,” would require strategies such as “emphasis on education regarding CV risk factors, improving access to quality healthcare, and facilitating lower-cost access to effective therapies for treatment of CV risk factors,” according to the researchers.

“Such advances need to be applied in a more equitable way throughout the United States, however,” they cautioned.
 

Census plus NHANES data

The researchers used 2020 U.S. census data and projected growth and 2013-2018 U.S. National Health and Nutrition Survey data to estimate the number of people with CV risk factors and CV disease from 2025 to 2060.

The estimates are based on a growing population and a fixed frequency.

Changing demographic landscape

It is “striking” that the numbers of non-White individuals with CV risk factors is projected to surpass the number of White individuals over time, and the number of non-White individuals with CV disease will be almost as many as White individuals by the year 2060, the editorialists noted.

“From a policy perspective, this means that unless appropriate, targeted action is taken, disparities in the burden of cardiovascular disease are only going to be exacerbated over time,” wrote Dr. Kalogeropoulos, from Stony Brook (N.Y.) University, and Dr. Butler, from Baylor College of Medicine, Dallas.

“On the positive side,” they continued, “the absolute increase in the percent prevalence of cardiovascular risk factors and conditions is projected to lie within a manageable range,” assuming that specific prevention policies are implemented.

“This is an opportunity for professional societies, including the cardiovascular care community, to re-evaluate priorities and strategies, for both training and practice, to best match the growing demands of a changing demographic landscape in the United States,” Dr. Kalogeropoulos and Dr. Butler concluded.

Dr. Mohebi is supported by the Barry Fellowship. Dr. Januzzi is supported by the Hutter Family Professorship; is a Trustee of the American College of Cardiology; is a board member of Imbria Pharmaceuticals; has received grant support from Abbott Diagnostics, Applied Therapeutics, Innolife, and Novartis; has received consulting income from Abbott Diagnostics, Boehringer Ingelheim, Janssen, Novartis, and Roche Diagnostics; and participates in clinical endpoint committees/data safety monitoring boards for AbbVie, Siemens, Takeda, and Vifor. Dr. Kalogeropoulos has received research funding from the National Heart, Lung, and Blood Institute; the American Heart Association; and the Centers for Disease Control and Prevention. Dr. Butler has been a consultant for numerous pharmaceutical companies.

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

A new analysis projects steep increases by 2060 in the prevalence of cardiovascular (CV) risk factors and disease that will disproportionately affect non-White populations who have limited access to health care.

The study by Reza Mohebi, MD, Massachusetts General Hospital and Harvard Medical School, both in Boston, and colleagues was published in the Journal of the American College of Cardiology.

“Even though several assumptions underlie these projections, the importance of this work cannot be overestimated,” Andreas P. Kalogeropoulos, MD, MPH, PhD, and Javed Butler, MD, MPH, MBA, wrote in an accompanying editorial. “The absolute numbers are staggering.”

From 2025 to 2060, the number of people with any one of four CV risk factors – type 2 diabetes, hypertension, dyslipidemia, and obesity – is projected to increase by 15.4 million, to 34.7 million.

And the number of people with of any one of four CV disease types – ischemic heart disease, heart failure, MI, and stroke – is projected to increase by 3.2 million, to 6.8 million.

Although the model predicts that the prevalence of CV risk factors will gradually decrease among White Americans, the highest prevalence of CV risk factors will be among the White population because of its overall size.

Conversely, the projected prevalence of CV risk factors is expected to increase in Black, Hispanic, Asian, and other race/ethnicity populations.

In parallel, the prevalence of CV disease is projected to decrease in the White population and increase among all other race/ethnicities, particularly in the Black and Hispanic populations.

Courtesy Massachusetts General Hospital

“Our results project a worrisome increase with a particularly ominous increase in risk factors and disease in our most vulnerable patients, including Blacks and Hispanics,” senior author James L. Januzzi Jr., MD, summarized in a video issued by the society.

“The steep rise in CV risk factors and disease reflects the generally higher prevalence in populations projected to increase in the United States, owing to immigration and growth, including Black or Hispanic individuals,” Dr. Januzzi, also from Massachusetts General and Harvard, said in an interview.

“The disproportionate size of the risk is expected in a sense, as minority populations are disproportionately disadvantaged with respect to their health care,” he said. “But whether it is expected or not, the increase in projected prevalence is, nonetheless, concerning and a call to action.”

This study identifies “areas of opportunity for change in the U.S. health care system,” he continued. “Business as usual will result in us encountering a huge number of individuals with CV risk factors and diseases.”

The results from the current analysis assume there will be no modification in health care policies or changes in access to care for at-risk populations, Dr. Mohebi and colleagues noted.

To “stem the rising tide of CV disease in at-risk individuals,” would require strategies such as “emphasis on education regarding CV risk factors, improving access to quality healthcare, and facilitating lower-cost access to effective therapies for treatment of CV risk factors,” according to the researchers.

“Such advances need to be applied in a more equitable way throughout the United States, however,” they cautioned.
 

Census plus NHANES data

The researchers used 2020 U.S. census data and projected growth and 2013-2018 U.S. National Health and Nutrition Survey data to estimate the number of people with CV risk factors and CV disease from 2025 to 2060.

The estimates are based on a growing population and a fixed frequency.

Changing demographic landscape

It is “striking” that the numbers of non-White individuals with CV risk factors is projected to surpass the number of White individuals over time, and the number of non-White individuals with CV disease will be almost as many as White individuals by the year 2060, the editorialists noted.

“From a policy perspective, this means that unless appropriate, targeted action is taken, disparities in the burden of cardiovascular disease are only going to be exacerbated over time,” wrote Dr. Kalogeropoulos, from Stony Brook (N.Y.) University, and Dr. Butler, from Baylor College of Medicine, Dallas.

“On the positive side,” they continued, “the absolute increase in the percent prevalence of cardiovascular risk factors and conditions is projected to lie within a manageable range,” assuming that specific prevention policies are implemented.

“This is an opportunity for professional societies, including the cardiovascular care community, to re-evaluate priorities and strategies, for both training and practice, to best match the growing demands of a changing demographic landscape in the United States,” Dr. Kalogeropoulos and Dr. Butler concluded.

Dr. Mohebi is supported by the Barry Fellowship. Dr. Januzzi is supported by the Hutter Family Professorship; is a Trustee of the American College of Cardiology; is a board member of Imbria Pharmaceuticals; has received grant support from Abbott Diagnostics, Applied Therapeutics, Innolife, and Novartis; has received consulting income from Abbott Diagnostics, Boehringer Ingelheim, Janssen, Novartis, and Roche Diagnostics; and participates in clinical endpoint committees/data safety monitoring boards for AbbVie, Siemens, Takeda, and Vifor. Dr. Kalogeropoulos has received research funding from the National Heart, Lung, and Blood Institute; the American Heart Association; and the Centers for Disease Control and Prevention. Dr. Butler has been a consultant for numerous pharmaceutical companies.

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

New COVID-19 vaccine boosters, targeting new Omicron strains of the virus, are expected to roll out across the United States in September – a month ahead of schedule, the Biden administration announced this week.

Moderna has signed a $1.74 billion federal contract to supply 66 million initial doses of the “bivalent” booster, which includes the original “ancestral” virus strain and elements of the Omicron BA.4 and BA.5 variants. Pfizer also announced a $3.2 billion U.S. agreement for another 105 million shots. Both vaccine suppliers have signed options to provide millions more boosters in the months ahead.

About 83.5% of Americans have received at least one COVID-19 shot, with 71.5% fully vaccinated with the initial series, 48% receiving one booster shot, and 31% two boosters, according to the CDC. With about 130,000 new COVID cases per day, and about 440 deaths, officials say the updated boosters may help rein in those figures by targeting the highly transmissible and widely circulating Omicron strains.

Federal health officials are still hammering out details of guidelines and recommendations of who should get the boosters, which are expected to come from the CDC and FDA. For now, authorities have decided not to expand eligibility for second boosters of the existing vaccines – now recommended only for adults over 50 and those 12 and older with immune deficiencies. Children 5 through 11 are advised to receive a single booster, 5 months after their initial vaccine series.

For a preview of what to expect from the CDC and FDA, this news organization spoke with Keri Althoff, PhD, an epidemiologist at Johns Hopkins University, Baltimore.
 

Q: Based on what we know now, who should be getting one of these new bivalent boosters?A: Of course, there is a process here regarding the specific recommendations, but it appears there will likely be a recommendation for all individuals to get this bivalent booster, similar to the first booster. And there will likely be a recommended time frame as to time since the last booster.

Right now, we have a recommendation for adults over the age of 50 or adults who are at higher risk for severe COVID-related illness [to get] a second booster. For them, there will probably be a timeline that says you should get the booster if you’re X amount of months or more from your second booster; or X amount of months or more from your first booster, if you’ve only had one.

Q: What about pregnant women or those being treated for chronic health conditions?A: I would imagine that once this bivalent booster becomes available, it will be recommended for all adults.

Q: And for children?A: That’s a good question. It’s something I have been digging into, [and] I think parents are really interested in this. Most kids, 5 and above, are supposed to be boosted with one shot right now, if they’re X amount of days from their primary vaccine series. Of course those 6 months to 4.99 years are not yet eligible [for boosters].

As a parent, I would love to see my children become eligible for the bivalent booster. It would be great if these boosters are conveying some additional protection that the kids could get access to before we send them off to school this fall. But there are questions as to whether or not that is going to happen.

Q: If you never received a booster, but only the preliminary vaccine series, do you need to get those earlier boosters before having the new bivalent booster shot?A: I don’t think they will likely make that a requirement – to restrict the bivalent booster only to those who are already boosted or up to date on their vaccines at the time the bivalent booster becomes available. But that will be up to the [CDC] vaccine recommendation committee to decide.

Q: Are there any new risks associated with these boosters, since they were developed so rapidly?A: No. We continue to monitor this technology, and with all the mRNA vaccines that have been delivered, you have seen all that monitoring play out with the detection, for example, of different forms of inflammation of the heart tissue and who that may impact. So, those monitoring systems work, and they work really, really well, so we can detect those things. And we know these vaccines are definitely safe.

Q: Some health experts are concerned “vaccine fatigue” will have an impact on the booster campaign. What’s your take?A: We have seen this fatigue in the proportion of individuals who are boosted with a first booster and even boosted with a second. But having those earlier boosters along with this new bivalent booster is important, because essentially, what we’re doing is really priming the immune system.

We’re trying to expedite the process of getting people’s immune system up to speed so that when the virus comes our way – as we know it will, because [of] these Omicron strains that are highly infectious and really whipping through our communities – we’re able to get the highest level of population immunity, you don’t end up in the hospital.

Q: What other challenges do you see in persuading Americans to get another round of boosters?A: One of the things that I’ve been hearing a lot, which I get very nervous about, is people saying: “Oh, I got fully vaccinated, I did or did not get the booster, and I had COVID anyway and it was really nothing, it didn’t feel like much to me, and so I’m not going to be boosted anymore.” We are not in a place quite yet where those guidelines are being rolled back in any way, shape, or form. We still have highly vulnerable people to severe disease and death in our communities, and we’re seeing hundreds of deaths every day.

There are consequences, even if it isn’t in severity of disease, meaning hospitalization and death. And let’s not let the actual quality of the vaccine being so successful that it can keep you out of the hospital. Don’t mistake that for “I don’t need another one.”

Q: Unlike the flu shot, which is reformulated each year to match circulating strains, the new COVID boosters offer protection against older strains as well as the newer ones. Why?A: It’s all about creating a broader immune response in individuals so that as more strains emerge, which they likely will, we can create a broader population immune response [to all strains]. Our individual bodies are seeing differences in these strains through vaccination that helps everyone stay healthy.

Q: There haven’t been clinical trials of these new mRNA boosters. How strong is the evidence that they will be effective against the emerging Omicron variants?A: There have been some studies – some great studies – looking at things like neutralizing antibodies, which we use as a surrogate for clinical trials. But that is not the same as studying the outcome of interest, which would be hospitalizations. So, part of the challenge is to be able to say: “Okay, this is what we know about the safety and effectiveness of the prior vaccines ... and how can we relate that to outcomes with these new boosters at an earlier stage [before] clinical data is available?”

Q: How long will the new boosters’ protections last – do we know yet?A: That timing is still a question, but of course what plays a big role in that is what COVID strains are circulating. If we prep these boosters that are Omicron specific, and then we have something totally new emerge ... we have to be more nimble because the variants are outpacing what we’re able to do.

This turns out to be a bit of a game of probability – the more infection we have, the more replication of the virus; the more replication, the more opportunity for mutations and subsequent variants.

Q: What about a combined flu-COVID vaccine; is that on the horizon?A: My children, who like most children do not like vaccines, always tell me: “Mom, why can’t they just put the influenza vaccine and the COVID vaccine into the same shot?” And I’m like: “Oh, from your lips to some scientist’s ears.”

At a time like this, where mRNA technology has totally disrupted what we can do with vaccines, in such a good way, I think we should push for the limits, because that would be incredible.

Q: If you’ve received a non-mRNA COVID vaccine, like those produced by Johnson & Johnson and Novavax, should you also get an mRNA booster?A: Right now, the CDC guidelines do state that if your primary vaccine series was not with an mRNA vaccine then being boosted with an mRNA is a fine thing to do, and it’s actually encouraged. So that’s not going to change with the bivalent booster.

Q: Is it okay to get a flu shot and a COVID booster at the same time, as the Centers for Disease Control and Prevention has recommended with past vaccines?A: I don’t anticipate there being recommendations against that. But I would also say watch for the recommendations that come out this fall on the bivalent boosters.

I do hope in the recommendations the CDC makes about the COVID boosters, they will say think about also getting your influenza vaccine, too. You could also get your COVID booster first, then by October get your influenza vaccine.

Q: Once you’re fully boosted, is it safe to stop wearing a mask, social distancing, avoiding crowded indoor spaces, and taking other precautions to avoid COVID-19?A: The virus is going to do what it does, which is infect whomever it can, and make them sick. So, if you see a lot of community transmission – you know who is ill with COVID in your kids’ schools, you know in your workplace and when people go out – that still signals there’s some increases in the circulation of virus. So, look at that to understand what your risk is.

If you know someone or have a colleague who is currently pregnant or immune suppressed, think about how you can protect them with mask-wearing, even if it’s just when you’re in one-on-one closed-door meetings with that individual.

So, your masking question is an important one, and it’s important for people to continue to hang onto those masks and wear them the week before you go see Grandma, for instance, to further reduce your risk so you don’t bring anything to here.

The high-level community risk nationwide is high right now. COVID is here.

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

New COVID-19 vaccine boosters, targeting new Omicron strains of the virus, are expected to roll out across the United States in September – a month ahead of schedule, the Biden administration announced this week.

Moderna has signed a $1.74 billion federal contract to supply 66 million initial doses of the “bivalent” booster, which includes the original “ancestral” virus strain and elements of the Omicron BA.4 and BA.5 variants. Pfizer also announced a $3.2 billion U.S. agreement for another 105 million shots. Both vaccine suppliers have signed options to provide millions more boosters in the months ahead.

About 83.5% of Americans have received at least one COVID-19 shot, with 71.5% fully vaccinated with the initial series, 48% receiving one booster shot, and 31% two boosters, according to the CDC. With about 130,000 new COVID cases per day, and about 440 deaths, officials say the updated boosters may help rein in those figures by targeting the highly transmissible and widely circulating Omicron strains.

Federal health officials are still hammering out details of guidelines and recommendations of who should get the boosters, which are expected to come from the CDC and FDA. For now, authorities have decided not to expand eligibility for second boosters of the existing vaccines – now recommended only for adults over 50 and those 12 and older with immune deficiencies. Children 5 through 11 are advised to receive a single booster, 5 months after their initial vaccine series.

For a preview of what to expect from the CDC and FDA, this news organization spoke with Keri Althoff, PhD, an epidemiologist at Johns Hopkins University, Baltimore.
 

Q: Based on what we know now, who should be getting one of these new bivalent boosters?A: Of course, there is a process here regarding the specific recommendations, but it appears there will likely be a recommendation for all individuals to get this bivalent booster, similar to the first booster. And there will likely be a recommended time frame as to time since the last booster.

Right now, we have a recommendation for adults over the age of 50 or adults who are at higher risk for severe COVID-related illness [to get] a second booster. For them, there will probably be a timeline that says you should get the booster if you’re X amount of months or more from your second booster; or X amount of months or more from your first booster, if you’ve only had one.

Q: What about pregnant women or those being treated for chronic health conditions?A: I would imagine that once this bivalent booster becomes available, it will be recommended for all adults.

Q: And for children?A: That’s a good question. It’s something I have been digging into, [and] I think parents are really interested in this. Most kids, 5 and above, are supposed to be boosted with one shot right now, if they’re X amount of days from their primary vaccine series. Of course those 6 months to 4.99 years are not yet eligible [for boosters].

As a parent, I would love to see my children become eligible for the bivalent booster. It would be great if these boosters are conveying some additional protection that the kids could get access to before we send them off to school this fall. But there are questions as to whether or not that is going to happen.

Q: If you never received a booster, but only the preliminary vaccine series, do you need to get those earlier boosters before having the new bivalent booster shot?A: I don’t think they will likely make that a requirement – to restrict the bivalent booster only to those who are already boosted or up to date on their vaccines at the time the bivalent booster becomes available. But that will be up to the [CDC] vaccine recommendation committee to decide.

Q: Are there any new risks associated with these boosters, since they were developed so rapidly?A: No. We continue to monitor this technology, and with all the mRNA vaccines that have been delivered, you have seen all that monitoring play out with the detection, for example, of different forms of inflammation of the heart tissue and who that may impact. So, those monitoring systems work, and they work really, really well, so we can detect those things. And we know these vaccines are definitely safe.

Q: Some health experts are concerned “vaccine fatigue” will have an impact on the booster campaign. What’s your take?A: We have seen this fatigue in the proportion of individuals who are boosted with a first booster and even boosted with a second. But having those earlier boosters along with this new bivalent booster is important, because essentially, what we’re doing is really priming the immune system.

We’re trying to expedite the process of getting people’s immune system up to speed so that when the virus comes our way – as we know it will, because [of] these Omicron strains that are highly infectious and really whipping through our communities – we’re able to get the highest level of population immunity, you don’t end up in the hospital.

Q: What other challenges do you see in persuading Americans to get another round of boosters?A: One of the things that I’ve been hearing a lot, which I get very nervous about, is people saying: “Oh, I got fully vaccinated, I did or did not get the booster, and I had COVID anyway and it was really nothing, it didn’t feel like much to me, and so I’m not going to be boosted anymore.” We are not in a place quite yet where those guidelines are being rolled back in any way, shape, or form. We still have highly vulnerable people to severe disease and death in our communities, and we’re seeing hundreds of deaths every day.

There are consequences, even if it isn’t in severity of disease, meaning hospitalization and death. And let’s not let the actual quality of the vaccine being so successful that it can keep you out of the hospital. Don’t mistake that for “I don’t need another one.”

Q: Unlike the flu shot, which is reformulated each year to match circulating strains, the new COVID boosters offer protection against older strains as well as the newer ones. Why?A: It’s all about creating a broader immune response in individuals so that as more strains emerge, which they likely will, we can create a broader population immune response [to all strains]. Our individual bodies are seeing differences in these strains through vaccination that helps everyone stay healthy.

Q: There haven’t been clinical trials of these new mRNA boosters. How strong is the evidence that they will be effective against the emerging Omicron variants?A: There have been some studies – some great studies – looking at things like neutralizing antibodies, which we use as a surrogate for clinical trials. But that is not the same as studying the outcome of interest, which would be hospitalizations. So, part of the challenge is to be able to say: “Okay, this is what we know about the safety and effectiveness of the prior vaccines ... and how can we relate that to outcomes with these new boosters at an earlier stage [before] clinical data is available?”

Q: How long will the new boosters’ protections last – do we know yet?A: That timing is still a question, but of course what plays a big role in that is what COVID strains are circulating. If we prep these boosters that are Omicron specific, and then we have something totally new emerge ... we have to be more nimble because the variants are outpacing what we’re able to do.

This turns out to be a bit of a game of probability – the more infection we have, the more replication of the virus; the more replication, the more opportunity for mutations and subsequent variants.

Q: What about a combined flu-COVID vaccine; is that on the horizon?A: My children, who like most children do not like vaccines, always tell me: “Mom, why can’t they just put the influenza vaccine and the COVID vaccine into the same shot?” And I’m like: “Oh, from your lips to some scientist’s ears.”

At a time like this, where mRNA technology has totally disrupted what we can do with vaccines, in such a good way, I think we should push for the limits, because that would be incredible.

Q: If you’ve received a non-mRNA COVID vaccine, like those produced by Johnson & Johnson and Novavax, should you also get an mRNA booster?A: Right now, the CDC guidelines do state that if your primary vaccine series was not with an mRNA vaccine then being boosted with an mRNA is a fine thing to do, and it’s actually encouraged. So that’s not going to change with the bivalent booster.

Q: Is it okay to get a flu shot and a COVID booster at the same time, as the Centers for Disease Control and Prevention has recommended with past vaccines?A: I don’t anticipate there being recommendations against that. But I would also say watch for the recommendations that come out this fall on the bivalent boosters.

I do hope in the recommendations the CDC makes about the COVID boosters, they will say think about also getting your influenza vaccine, too. You could also get your COVID booster first, then by October get your influenza vaccine.

Q: Once you’re fully boosted, is it safe to stop wearing a mask, social distancing, avoiding crowded indoor spaces, and taking other precautions to avoid COVID-19?A: The virus is going to do what it does, which is infect whomever it can, and make them sick. So, if you see a lot of community transmission – you know who is ill with COVID in your kids’ schools, you know in your workplace and when people go out – that still signals there’s some increases in the circulation of virus. So, look at that to understand what your risk is.

If you know someone or have a colleague who is currently pregnant or immune suppressed, think about how you can protect them with mask-wearing, even if it’s just when you’re in one-on-one closed-door meetings with that individual.

So, your masking question is an important one, and it’s important for people to continue to hang onto those masks and wear them the week before you go see Grandma, for instance, to further reduce your risk so you don’t bring anything to here.

The high-level community risk nationwide is high right now. COVID is here.

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

New COVID-19 vaccine boosters, targeting new Omicron strains of the virus, are expected to roll out across the United States in September – a month ahead of schedule, the Biden administration announced this week.

Moderna has signed a $1.74 billion federal contract to supply 66 million initial doses of the “bivalent” booster, which includes the original “ancestral” virus strain and elements of the Omicron BA.4 and BA.5 variants. Pfizer also announced a $3.2 billion U.S. agreement for another 105 million shots. Both vaccine suppliers have signed options to provide millions more boosters in the months ahead.

About 83.5% of Americans have received at least one COVID-19 shot, with 71.5% fully vaccinated with the initial series, 48% receiving one booster shot, and 31% two boosters, according to the CDC. With about 130,000 new COVID cases per day, and about 440 deaths, officials say the updated boosters may help rein in those figures by targeting the highly transmissible and widely circulating Omicron strains.

Federal health officials are still hammering out details of guidelines and recommendations of who should get the boosters, which are expected to come from the CDC and FDA. For now, authorities have decided not to expand eligibility for second boosters of the existing vaccines – now recommended only for adults over 50 and those 12 and older with immune deficiencies. Children 5 through 11 are advised to receive a single booster, 5 months after their initial vaccine series.

For a preview of what to expect from the CDC and FDA, this news organization spoke with Keri Althoff, PhD, an epidemiologist at Johns Hopkins University, Baltimore.
 

Q: Based on what we know now, who should be getting one of these new bivalent boosters?A: Of course, there is a process here regarding the specific recommendations, but it appears there will likely be a recommendation for all individuals to get this bivalent booster, similar to the first booster. And there will likely be a recommended time frame as to time since the last booster.

Right now, we have a recommendation for adults over the age of 50 or adults who are at higher risk for severe COVID-related illness [to get] a second booster. For them, there will probably be a timeline that says you should get the booster if you’re X amount of months or more from your second booster; or X amount of months or more from your first booster, if you’ve only had one.

Q: What about pregnant women or those being treated for chronic health conditions?A: I would imagine that once this bivalent booster becomes available, it will be recommended for all adults.

Q: And for children?A: That’s a good question. It’s something I have been digging into, [and] I think parents are really interested in this. Most kids, 5 and above, are supposed to be boosted with one shot right now, if they’re X amount of days from their primary vaccine series. Of course those 6 months to 4.99 years are not yet eligible [for boosters].

As a parent, I would love to see my children become eligible for the bivalent booster. It would be great if these boosters are conveying some additional protection that the kids could get access to before we send them off to school this fall. But there are questions as to whether or not that is going to happen.

Q: If you never received a booster, but only the preliminary vaccine series, do you need to get those earlier boosters before having the new bivalent booster shot?A: I don’t think they will likely make that a requirement – to restrict the bivalent booster only to those who are already boosted or up to date on their vaccines at the time the bivalent booster becomes available. But that will be up to the [CDC] vaccine recommendation committee to decide.

Q: Are there any new risks associated with these boosters, since they were developed so rapidly?A: No. We continue to monitor this technology, and with all the mRNA vaccines that have been delivered, you have seen all that monitoring play out with the detection, for example, of different forms of inflammation of the heart tissue and who that may impact. So, those monitoring systems work, and they work really, really well, so we can detect those things. And we know these vaccines are definitely safe.

Q: Some health experts are concerned “vaccine fatigue” will have an impact on the booster campaign. What’s your take?A: We have seen this fatigue in the proportion of individuals who are boosted with a first booster and even boosted with a second. But having those earlier boosters along with this new bivalent booster is important, because essentially, what we’re doing is really priming the immune system.

We’re trying to expedite the process of getting people’s immune system up to speed so that when the virus comes our way – as we know it will, because [of] these Omicron strains that are highly infectious and really whipping through our communities – we’re able to get the highest level of population immunity, you don’t end up in the hospital.

Q: What other challenges do you see in persuading Americans to get another round of boosters?A: One of the things that I’ve been hearing a lot, which I get very nervous about, is people saying: “Oh, I got fully vaccinated, I did or did not get the booster, and I had COVID anyway and it was really nothing, it didn’t feel like much to me, and so I’m not going to be boosted anymore.” We are not in a place quite yet where those guidelines are being rolled back in any way, shape, or form. We still have highly vulnerable people to severe disease and death in our communities, and we’re seeing hundreds of deaths every day.

There are consequences, even if it isn’t in severity of disease, meaning hospitalization and death. And let’s not let the actual quality of the vaccine being so successful that it can keep you out of the hospital. Don’t mistake that for “I don’t need another one.”

Q: Unlike the flu shot, which is reformulated each year to match circulating strains, the new COVID boosters offer protection against older strains as well as the newer ones. Why?A: It’s all about creating a broader immune response in individuals so that as more strains emerge, which they likely will, we can create a broader population immune response [to all strains]. Our individual bodies are seeing differences in these strains through vaccination that helps everyone stay healthy.

Q: There haven’t been clinical trials of these new mRNA boosters. How strong is the evidence that they will be effective against the emerging Omicron variants?A: There have been some studies – some great studies – looking at things like neutralizing antibodies, which we use as a surrogate for clinical trials. But that is not the same as studying the outcome of interest, which would be hospitalizations. So, part of the challenge is to be able to say: “Okay, this is what we know about the safety and effectiveness of the prior vaccines ... and how can we relate that to outcomes with these new boosters at an earlier stage [before] clinical data is available?”

Q: How long will the new boosters’ protections last – do we know yet?A: That timing is still a question, but of course what plays a big role in that is what COVID strains are circulating. If we prep these boosters that are Omicron specific, and then we have something totally new emerge ... we have to be more nimble because the variants are outpacing what we’re able to do.

This turns out to be a bit of a game of probability – the more infection we have, the more replication of the virus; the more replication, the more opportunity for mutations and subsequent variants.

Q: What about a combined flu-COVID vaccine; is that on the horizon?A: My children, who like most children do not like vaccines, always tell me: “Mom, why can’t they just put the influenza vaccine and the COVID vaccine into the same shot?” And I’m like: “Oh, from your lips to some scientist’s ears.”

At a time like this, where mRNA technology has totally disrupted what we can do with vaccines, in such a good way, I think we should push for the limits, because that would be incredible.

Q: If you’ve received a non-mRNA COVID vaccine, like those produced by Johnson & Johnson and Novavax, should you also get an mRNA booster?A: Right now, the CDC guidelines do state that if your primary vaccine series was not with an mRNA vaccine then being boosted with an mRNA is a fine thing to do, and it’s actually encouraged. So that’s not going to change with the bivalent booster.

Q: Is it okay to get a flu shot and a COVID booster at the same time, as the Centers for Disease Control and Prevention has recommended with past vaccines?A: I don’t anticipate there being recommendations against that. But I would also say watch for the recommendations that come out this fall on the bivalent boosters.

I do hope in the recommendations the CDC makes about the COVID boosters, they will say think about also getting your influenza vaccine, too. You could also get your COVID booster first, then by October get your influenza vaccine.

Q: Once you’re fully boosted, is it safe to stop wearing a mask, social distancing, avoiding crowded indoor spaces, and taking other precautions to avoid COVID-19?A: The virus is going to do what it does, which is infect whomever it can, and make them sick. So, if you see a lot of community transmission – you know who is ill with COVID in your kids’ schools, you know in your workplace and when people go out – that still signals there’s some increases in the circulation of virus. So, look at that to understand what your risk is.

If you know someone or have a colleague who is currently pregnant or immune suppressed, think about how you can protect them with mask-wearing, even if it’s just when you’re in one-on-one closed-door meetings with that individual.

So, your masking question is an important one, and it’s important for people to continue to hang onto those masks and wear them the week before you go see Grandma, for instance, to further reduce your risk so you don’t bring anything to here.

The high-level community risk nationwide is high right now. COVID is here.

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

Human papillomavirus (HPV) vaccine given around the time women have surgery for precancerous cervical lesions might lead to a reduction in the risk of lesions returning, as well as other HPV-related diseases, but the effects of this remain unclear.

The authors of the new study, published in The BMJ, explained that women who have been treated for high-grade cervical intra-epithelial neoplasia (CIN) have a “lifelong residual high risk of cervical cancer and other malignancies related to HPV infection,” and some research suggests that giving a preventive HPV vaccine alongside treatment for CIN might help to “reduce the risk in these women.”

HPV vaccination is highly effective at preventing the development of precancerous cervical lesions, CIN, and in the U.K., HPV vaccination is offered to girls and boys around the age of 12 or 13.

Eluned Hughes, head of information and engagement at Jo’s Cervical Cancer Trust, said: “Recent evidence has found that cases of cervical cancer have fallen 87% since the introduction of the HPV vaccine program in U.K. schools in 2008.”

“However, women over the age of 27, for whom the vaccine was not available, remain at increased risk of cervical cancer,” she highlighted.
 

Significant risk of bias and scarcity of data

In the study, researchers set out to explore the efficacy of HPV vaccination on the risk of HPV infection and recurrent diseases related to HPV infection in individuals undergoing local surgical treatment of preinvasive genital disease.

The systematic review and meta-analysis, led by researchers at Imperial College London, screened data from PubMed (Medline), Scopus, Cochrane, Web of Science, and ClinicalTrials.gov from inception to March 31, 2021.

The researchers analyzed the results of 18 studies – two randomized controlled trials (RCTs), 12 observational studies, and four post-hoc analyses of RCTs.

The authors said that the two RCTs were classified as low risk of bias, while in the observational studies and post-hoc analyses, risk of bias was moderate for seven, serious for seven, and critical for two. Average length of follow-up was 36 months.

There was a reduction of 57% in the risk of recurrence of high-grade pre-invasive disease (CIN2+) in individuals who were vaccinated, compared with those who were not vaccinated. “The effect estimate was “even more pronounced” – a relative 74% reduction – when the risk of recurrence of CIN2+ was assessed for disease related to the two high-risk HPV types – HPV16 and HPV18,” explained the authors.

However, the researchers noted that these effects are unclear because of the “scarcity of data” and the “moderate to high overall risk of bias” of the available studies.
 

Quality of evidence inconclusive – more trials needed

With regards to CIN3, the risk of recurrence of was also reduced in patients who were vaccinated, but there was a high level of uncertainty about the quality of this evidence, cautioned the authors.

Evidence was also lacking on the benefit of HPV vaccination for recurrence of vulvar, vaginal, and anal lesions, as well as genital warts.

Analysis of the post-hoc studies from randomized controlled trial data with historic vaccination at randomization before the development of the disease reported inconsistent results, the authors said.

Several study limitations were acknowledged by the authors, including that most of the studies were observational, of low to moderate quality, and with relatively short follow-up times, which they pointed out prevented assessment of long-term effects. In addition, the average age of participants was not provided in most studies, and factors such as smoking – associated with a higher risk of recurrence – were not controlled for in many studies.

“HPV vaccination might reduce the risk of recurrence of CIN, in particular when related to HPV16 or HPV18, in women treated with local excision,” they concluded. However, they cautioned that “quality of evidence indicated that the data were inconclusive.”

“Large, appropriately powered, randomized controlled trials are required to establish the effectiveness of adjuvant HPV vaccination at the time of local surgical treatment of CIN,” they recommended.

“Given that the incidence of recurrence of high-grade disease is low in quality assured national screening programs, such as in the United Kingdom, absolute risks and a cost effectiveness analysis would be important in determining the implementation strategy of HPV vaccination after treatment,” the authors said.

Ms. Hughes said that the charity was pleased to see emerging research into the value of using the HPV vaccine to prevent the recurrence of cervical cell changes. She said that the charity looks forward to seeing “further large-scale studies into the effectiveness of this method.”

In the meantime, the charity encourages all women and other people with a cervix to attend their cervical screening and for young people to have the HPV vaccination when invited, as “these are the best tools we currently have to prevent cervical cancer,” she said.

A version of this article first appeared on Medscape UK.

Human papillomavirus (HPV) vaccine given around the time women have surgery for precancerous cervical lesions might lead to a reduction in the risk of lesions returning, as well as other HPV-related diseases, but the effects of this remain unclear.

The authors of the new study, published in The BMJ, explained that women who have been treated for high-grade cervical intra-epithelial neoplasia (CIN) have a “lifelong residual high risk of cervical cancer and other malignancies related to HPV infection,” and some research suggests that giving a preventive HPV vaccine alongside treatment for CIN might help to “reduce the risk in these women.”

HPV vaccination is highly effective at preventing the development of precancerous cervical lesions, CIN, and in the U.K., HPV vaccination is offered to girls and boys around the age of 12 or 13.

Eluned Hughes, head of information and engagement at Jo’s Cervical Cancer Trust, said: “Recent evidence has found that cases of cervical cancer have fallen 87% since the introduction of the HPV vaccine program in U.K. schools in 2008.”

“However, women over the age of 27, for whom the vaccine was not available, remain at increased risk of cervical cancer,” she highlighted.
 

Significant risk of bias and scarcity of data

In the study, researchers set out to explore the efficacy of HPV vaccination on the risk of HPV infection and recurrent diseases related to HPV infection in individuals undergoing local surgical treatment of preinvasive genital disease.

The systematic review and meta-analysis, led by researchers at Imperial College London, screened data from PubMed (Medline), Scopus, Cochrane, Web of Science, and ClinicalTrials.gov from inception to March 31, 2021.

The researchers analyzed the results of 18 studies – two randomized controlled trials (RCTs), 12 observational studies, and four post-hoc analyses of RCTs.

The authors said that the two RCTs were classified as low risk of bias, while in the observational studies and post-hoc analyses, risk of bias was moderate for seven, serious for seven, and critical for two. Average length of follow-up was 36 months.

There was a reduction of 57% in the risk of recurrence of high-grade pre-invasive disease (CIN2+) in individuals who were vaccinated, compared with those who were not vaccinated. “The effect estimate was “even more pronounced” – a relative 74% reduction – when the risk of recurrence of CIN2+ was assessed for disease related to the two high-risk HPV types – HPV16 and HPV18,” explained the authors.

However, the researchers noted that these effects are unclear because of the “scarcity of data” and the “moderate to high overall risk of bias” of the available studies.
 

Quality of evidence inconclusive – more trials needed

With regards to CIN3, the risk of recurrence of was also reduced in patients who were vaccinated, but there was a high level of uncertainty about the quality of this evidence, cautioned the authors.

Evidence was also lacking on the benefit of HPV vaccination for recurrence of vulvar, vaginal, and anal lesions, as well as genital warts.

Analysis of the post-hoc studies from randomized controlled trial data with historic vaccination at randomization before the development of the disease reported inconsistent results, the authors said.

Several study limitations were acknowledged by the authors, including that most of the studies were observational, of low to moderate quality, and with relatively short follow-up times, which they pointed out prevented assessment of long-term effects. In addition, the average age of participants was not provided in most studies, and factors such as smoking – associated with a higher risk of recurrence – were not controlled for in many studies.

“HPV vaccination might reduce the risk of recurrence of CIN, in particular when related to HPV16 or HPV18, in women treated with local excision,” they concluded. However, they cautioned that “quality of evidence indicated that the data were inconclusive.”

“Large, appropriately powered, randomized controlled trials are required to establish the effectiveness of adjuvant HPV vaccination at the time of local surgical treatment of CIN,” they recommended.

“Given that the incidence of recurrence of high-grade disease is low in quality assured national screening programs, such as in the United Kingdom, absolute risks and a cost effectiveness analysis would be important in determining the implementation strategy of HPV vaccination after treatment,” the authors said.

Ms. Hughes said that the charity was pleased to see emerging research into the value of using the HPV vaccine to prevent the recurrence of cervical cell changes. She said that the charity looks forward to seeing “further large-scale studies into the effectiveness of this method.”

In the meantime, the charity encourages all women and other people with a cervix to attend their cervical screening and for young people to have the HPV vaccination when invited, as “these are the best tools we currently have to prevent cervical cancer,” she said.

A version of this article first appeared on Medscape UK.

Human papillomavirus (HPV) vaccine given around the time women have surgery for precancerous cervical lesions might lead to a reduction in the risk of lesions returning, as well as other HPV-related diseases, but the effects of this remain unclear.

The authors of the new study, published in The BMJ, explained that women who have been treated for high-grade cervical intra-epithelial neoplasia (CIN) have a “lifelong residual high risk of cervical cancer and other malignancies related to HPV infection,” and some research suggests that giving a preventive HPV vaccine alongside treatment for CIN might help to “reduce the risk in these women.”

HPV vaccination is highly effective at preventing the development of precancerous cervical lesions, CIN, and in the U.K., HPV vaccination is offered to girls and boys around the age of 12 or 13.

Eluned Hughes, head of information and engagement at Jo’s Cervical Cancer Trust, said: “Recent evidence has found that cases of cervical cancer have fallen 87% since the introduction of the HPV vaccine program in U.K. schools in 2008.”

“However, women over the age of 27, for whom the vaccine was not available, remain at increased risk of cervical cancer,” she highlighted.
 

Significant risk of bias and scarcity of data

In the study, researchers set out to explore the efficacy of HPV vaccination on the risk of HPV infection and recurrent diseases related to HPV infection in individuals undergoing local surgical treatment of preinvasive genital disease.

The systematic review and meta-analysis, led by researchers at Imperial College London, screened data from PubMed (Medline), Scopus, Cochrane, Web of Science, and ClinicalTrials.gov from inception to March 31, 2021.

The researchers analyzed the results of 18 studies – two randomized controlled trials (RCTs), 12 observational studies, and four post-hoc analyses of RCTs.

The authors said that the two RCTs were classified as low risk of bias, while in the observational studies and post-hoc analyses, risk of bias was moderate for seven, serious for seven, and critical for two. Average length of follow-up was 36 months.

There was a reduction of 57% in the risk of recurrence of high-grade pre-invasive disease (CIN2+) in individuals who were vaccinated, compared with those who were not vaccinated. “The effect estimate was “even more pronounced” – a relative 74% reduction – when the risk of recurrence of CIN2+ was assessed for disease related to the two high-risk HPV types – HPV16 and HPV18,” explained the authors.

However, the researchers noted that these effects are unclear because of the “scarcity of data” and the “moderate to high overall risk of bias” of the available studies.
 

Quality of evidence inconclusive – more trials needed

With regards to CIN3, the risk of recurrence of was also reduced in patients who were vaccinated, but there was a high level of uncertainty about the quality of this evidence, cautioned the authors.

Evidence was also lacking on the benefit of HPV vaccination for recurrence of vulvar, vaginal, and anal lesions, as well as genital warts.

Analysis of the post-hoc studies from randomized controlled trial data with historic vaccination at randomization before the development of the disease reported inconsistent results, the authors said.

Several study limitations were acknowledged by the authors, including that most of the studies were observational, of low to moderate quality, and with relatively short follow-up times, which they pointed out prevented assessment of long-term effects. In addition, the average age of participants was not provided in most studies, and factors such as smoking – associated with a higher risk of recurrence – were not controlled for in many studies.

“HPV vaccination might reduce the risk of recurrence of CIN, in particular when related to HPV16 or HPV18, in women treated with local excision,” they concluded. However, they cautioned that “quality of evidence indicated that the data were inconclusive.”

“Large, appropriately powered, randomized controlled trials are required to establish the effectiveness of adjuvant HPV vaccination at the time of local surgical treatment of CIN,” they recommended.

“Given that the incidence of recurrence of high-grade disease is low in quality assured national screening programs, such as in the United Kingdom, absolute risks and a cost effectiveness analysis would be important in determining the implementation strategy of HPV vaccination after treatment,” the authors said.

Ms. Hughes said that the charity was pleased to see emerging research into the value of using the HPV vaccine to prevent the recurrence of cervical cell changes. She said that the charity looks forward to seeing “further large-scale studies into the effectiveness of this method.”

In the meantime, the charity encourages all women and other people with a cervix to attend their cervical screening and for young people to have the HPV vaccination when invited, as “these are the best tools we currently have to prevent cervical cancer,” she said.

A version of this article first appeared on Medscape UK.

Regular exercise, regardless of intensity level, appears to slow cognitive decline in sedentary older adults with mild cognitive impariment (MCI), new research from the largest study of its kind suggests. Topline results from the EXERT trial showed patients with MCI who participated regularly in either aerobic exercise or stretching/balance/range-of-motion exercises maintained stable global cognitive function over 12 months of follow-up – with no differences between the two types of exercise.

“We’re excited about these findings, because these types of exercises that we’re seeing can protect against cognitive decline are accessible to everyone and therefore scalable to the public,” study investigator Laura Baker, PhD, Wake Forest University School of Medicine, Winston-Salem, N.C., said at a press briefing.

The topline results were presented at the 2022 Alzheimer’s Association International Conference.
 

No decline

The 18-month EXERT trial was designed to be the definitive study to answer the question about whether exercise can slow cognitive decline in older adults with amnestic MCI, Dr. Baker reported. Investigators enrolled 296 sedentary men and women with MCI (mean age, about 75 years). All were randomly allocated to either an aerobic exercise group (maintaining a heart rate at about 70%-85%) or a stretching and balance group (maintaining heart rate less than 35%).

Both groups exercised four times per week for about 30-40 minutes. In the first 12 months they were supervised by a trainer at the YMCA and then they exercised independently for the final 6 months.

Participants were assessed at baseline and every 6 months. The primary endpoint was change from baseline on the ADAS-Cog-Exec, a validated measure of global cognitive function, at the end of the 12 months of supervised exercise.

During the first 12 months, participants completed over 31,000 sessions of exercise, which is “quite impressive,” Dr. Baker said.

Over the first 12 months, neither the aerobic group nor the stretch/balance group showed a decline on the ADAS-Cog-Exec.

“We saw no group differences, and importantly, no decline after 12 months,” Dr. Baker reported.
 

Supported exercise is ‘crucial’

To help “make sense” of these findings, Dr. Baker noted that 12-month changes in the ADAS-Cog-Exec for the EXERT intervention groups were also compared with a “usual care” cohort of adults matched for age, sex, education, baseline cognitive status, and APOE4 genotype.

In this “apples-to-apples” comparison, the usual care cohort showed the expected decline or worsening of cognitive function over 12 months on the ADAS-Cog-Exec, but the EXERT exercise groups did not.

Dr. Baker noted that both exercise groups received equal amounts of weekly socialization, which may have contributed to the apparent protective effects on the brain.

A greater volume of exercise in EXERT, compared with other trials, may also be a factor. Each individual participant in EXERT completed more than 100 hours of exercise.

“The take-home message is that an increased amount of either low-intensity or high-intensity exercise for 120-150 minutes per week for 12 months may slow cognitive decline in sedentary older adults with MCI,” Dr. Baker said.

“What’s critical is that this regular exercise must be supported in these older [patients] with MCI. It must be supervised. There has to be some social component,” she added.

In her view, 120 minutes of regular supported exercise for sedentary individuals with MCI “needs to be part of the recommendation for risk reduction.”
 

Important study

Commenting on the findings, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, noted that several studies over the years have suggested that different types of exercise can have benefits on the brain.

“What’s important about this study is that it’s in a population of people that have MCI and are already experiencing memory changes,” Dr. Snyder said.

“The results suggest that engaging in both of these types of exercise may be beneficial for our brain. And given that this is the largest study of its kind in a population of people with MCI, it suggests it’s ‘never too late’ to start exercising,” she added.

Dr. Snyder noted the importance of continuing this work and to continue following these individuals “over time as well.”

The study was funded by the National Institutes of Health, National Institute on Aging. Dr. Baker and Dr. Snyder have disclosed no relevant financial relationships.

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

Regular exercise, regardless of intensity level, appears to slow cognitive decline in sedentary older adults with mild cognitive impariment (MCI), new research from the largest study of its kind suggests. Topline results from the EXERT trial showed patients with MCI who participated regularly in either aerobic exercise or stretching/balance/range-of-motion exercises maintained stable global cognitive function over 12 months of follow-up – with no differences between the two types of exercise.

“We’re excited about these findings, because these types of exercises that we’re seeing can protect against cognitive decline are accessible to everyone and therefore scalable to the public,” study investigator Laura Baker, PhD, Wake Forest University School of Medicine, Winston-Salem, N.C., said at a press briefing.

The topline results were presented at the 2022 Alzheimer’s Association International Conference.
 

No decline

The 18-month EXERT trial was designed to be the definitive study to answer the question about whether exercise can slow cognitive decline in older adults with amnestic MCI, Dr. Baker reported. Investigators enrolled 296 sedentary men and women with MCI (mean age, about 75 years). All were randomly allocated to either an aerobic exercise group (maintaining a heart rate at about 70%-85%) or a stretching and balance group (maintaining heart rate less than 35%).

Both groups exercised four times per week for about 30-40 minutes. In the first 12 months they were supervised by a trainer at the YMCA and then they exercised independently for the final 6 months.

Participants were assessed at baseline and every 6 months. The primary endpoint was change from baseline on the ADAS-Cog-Exec, a validated measure of global cognitive function, at the end of the 12 months of supervised exercise.

During the first 12 months, participants completed over 31,000 sessions of exercise, which is “quite impressive,” Dr. Baker said.

Over the first 12 months, neither the aerobic group nor the stretch/balance group showed a decline on the ADAS-Cog-Exec.

“We saw no group differences, and importantly, no decline after 12 months,” Dr. Baker reported.
 

Supported exercise is ‘crucial’

To help “make sense” of these findings, Dr. Baker noted that 12-month changes in the ADAS-Cog-Exec for the EXERT intervention groups were also compared with a “usual care” cohort of adults matched for age, sex, education, baseline cognitive status, and APOE4 genotype.

In this “apples-to-apples” comparison, the usual care cohort showed the expected decline or worsening of cognitive function over 12 months on the ADAS-Cog-Exec, but the EXERT exercise groups did not.

Dr. Baker noted that both exercise groups received equal amounts of weekly socialization, which may have contributed to the apparent protective effects on the brain.

A greater volume of exercise in EXERT, compared with other trials, may also be a factor. Each individual participant in EXERT completed more than 100 hours of exercise.

“The take-home message is that an increased amount of either low-intensity or high-intensity exercise for 120-150 minutes per week for 12 months may slow cognitive decline in sedentary older adults with MCI,” Dr. Baker said.

“What’s critical is that this regular exercise must be supported in these older [patients] with MCI. It must be supervised. There has to be some social component,” she added.

In her view, 120 minutes of regular supported exercise for sedentary individuals with MCI “needs to be part of the recommendation for risk reduction.”
 

Important study

Commenting on the findings, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, noted that several studies over the years have suggested that different types of exercise can have benefits on the brain.

“What’s important about this study is that it’s in a population of people that have MCI and are already experiencing memory changes,” Dr. Snyder said.

“The results suggest that engaging in both of these types of exercise may be beneficial for our brain. And given that this is the largest study of its kind in a population of people with MCI, it suggests it’s ‘never too late’ to start exercising,” she added.

Dr. Snyder noted the importance of continuing this work and to continue following these individuals “over time as well.”

The study was funded by the National Institutes of Health, National Institute on Aging. Dr. Baker and Dr. Snyder have disclosed no relevant financial relationships.

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

Regular exercise, regardless of intensity level, appears to slow cognitive decline in sedentary older adults with mild cognitive impariment (MCI), new research from the largest study of its kind suggests. Topline results from the EXERT trial showed patients with MCI who participated regularly in either aerobic exercise or stretching/balance/range-of-motion exercises maintained stable global cognitive function over 12 months of follow-up – with no differences between the two types of exercise.

“We’re excited about these findings, because these types of exercises that we’re seeing can protect against cognitive decline are accessible to everyone and therefore scalable to the public,” study investigator Laura Baker, PhD, Wake Forest University School of Medicine, Winston-Salem, N.C., said at a press briefing.

The topline results were presented at the 2022 Alzheimer’s Association International Conference.
 

No decline

The 18-month EXERT trial was designed to be the definitive study to answer the question about whether exercise can slow cognitive decline in older adults with amnestic MCI, Dr. Baker reported. Investigators enrolled 296 sedentary men and women with MCI (mean age, about 75 years). All were randomly allocated to either an aerobic exercise group (maintaining a heart rate at about 70%-85%) or a stretching and balance group (maintaining heart rate less than 35%).

Both groups exercised four times per week for about 30-40 minutes. In the first 12 months they were supervised by a trainer at the YMCA and then they exercised independently for the final 6 months.

Participants were assessed at baseline and every 6 months. The primary endpoint was change from baseline on the ADAS-Cog-Exec, a validated measure of global cognitive function, at the end of the 12 months of supervised exercise.

During the first 12 months, participants completed over 31,000 sessions of exercise, which is “quite impressive,” Dr. Baker said.

Over the first 12 months, neither the aerobic group nor the stretch/balance group showed a decline on the ADAS-Cog-Exec.

“We saw no group differences, and importantly, no decline after 12 months,” Dr. Baker reported.
 

Supported exercise is ‘crucial’

To help “make sense” of these findings, Dr. Baker noted that 12-month changes in the ADAS-Cog-Exec for the EXERT intervention groups were also compared with a “usual care” cohort of adults matched for age, sex, education, baseline cognitive status, and APOE4 genotype.

In this “apples-to-apples” comparison, the usual care cohort showed the expected decline or worsening of cognitive function over 12 months on the ADAS-Cog-Exec, but the EXERT exercise groups did not.

Dr. Baker noted that both exercise groups received equal amounts of weekly socialization, which may have contributed to the apparent protective effects on the brain.

A greater volume of exercise in EXERT, compared with other trials, may also be a factor. Each individual participant in EXERT completed more than 100 hours of exercise.

“The take-home message is that an increased amount of either low-intensity or high-intensity exercise for 120-150 minutes per week for 12 months may slow cognitive decline in sedentary older adults with MCI,” Dr. Baker said.

“What’s critical is that this regular exercise must be supported in these older [patients] with MCI. It must be supervised. There has to be some social component,” she added.

In her view, 120 minutes of regular supported exercise for sedentary individuals with MCI “needs to be part of the recommendation for risk reduction.”
 

Important study

Commenting on the findings, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, noted that several studies over the years have suggested that different types of exercise can have benefits on the brain.

“What’s important about this study is that it’s in a population of people that have MCI and are already experiencing memory changes,” Dr. Snyder said.

“The results suggest that engaging in both of these types of exercise may be beneficial for our brain. And given that this is the largest study of its kind in a population of people with MCI, it suggests it’s ‘never too late’ to start exercising,” she added.

Dr. Snyder noted the importance of continuing this work and to continue following these individuals “over time as well.”

The study was funded by the National Institutes of Health, National Institute on Aging. Dr. Baker and Dr. Snyder have disclosed no relevant financial relationships.

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

When Joel Fram woke up on the morning of March 12, 2020, he had a pretty good idea why he felt so lousy.

He lives in New York, where the first wave of the coronavirus was tearing through the city. “I instantly knew,” said the 55-year-old Broadway music director. It was COVID-19.

What started with a general sense of having been hit by a truck soon included a sore throat and such severe fatigue that he once fell asleep in the middle of sending a text to his sister. The final symptoms were chest tightness and trouble breathing.

And then he started to feel better. “By mid-April, my body was feeling essentially back to normal,” he said.

So he did what would have been smart after almost any other illness: He began working out. That didn’t last long. “It felt like someone pulled the carpet out from under me,” he remembered. “I couldn’t walk three blocks without getting breathless and fatigued.”

That was the first indication Mr. Fram had long COVID.

According to the National Center for Health Statistics, at least 7.5% of American adults – close to 20 million people – have symptoms of long COVID. And for almost all of those people, a growing body of evidence shows that exercise will make their symptoms worse.

COVID-19 patients who had the most severe illness will struggle the most with exercise later, according to a review published in June from researchers at the University of California, San Francisco. But even people with mild symptoms can struggle to regain their previous levels of fitness.

“We have participants in our study who had relatively mild acute symptoms and went on to have really profound decreases in their ability to exercise,” said Matthew S. Durstenfeld, MD, a cardiologist at UCSF and principal author of the review.

Most people with long COVID will have lower-than-expected scores on tests of aerobic fitness, as shown by Yale researchers in a study published in August 2021.

“Some amount of that is due to deconditioning,” Dr. Durstenfeld said. “You’re not feeling well, so you’re not exercising to the same degree you might have been before you got infected.”

In a study published in April, people with long COVID told researchers at Britain’s University of Leeds they spent 93% less time in physical activity than they did before their infection.

But multiple studies have found deconditioning is not entirely – or even mostly – to blame.

A 2021 study found that 89% of participants with long COVID had postexertional malaise (PEM), which happens when a patient’s symptoms get worse after they do even minor physical or mental activities. According to the CDC, postexertional malaise can hit as long as 12-48 hours after the activity, and it can take people up to 2 weeks to fully recover.

Unfortunately, the advice patients get from their doctors sometimes makes the problem worse.
 

How long COVID defies simple solutions

Long COVID is a “dynamic disability” that requires health professionals to go off script when a patient’s symptoms don’t respond in a predictable way to treatment, said David Putrino, PhD, a neuroscientist, physical therapist, and director of rehabilitation innovation for the Mount Sinai Health System in New York.

“We’re not so good at dealing with somebody who, for all intents and purposes, can appear healthy and nondisabled on one day and be completely debilitated the next day,” he said.

Dr. Putrino said more than half of his clinic’s long-COVID patients told his team they had at least one of these persistent problems:

• Fatigue (82%).
• Brain fog (67%).
• Headache (60%).
• Sleep problems (59%).
• Dizziness (54%).

And 86% said exercise worsened their symptoms.

The symptoms are similar to what doctors see with illnesses such as lupus, Lyme disease, and chronic fatigue syndrome – something many experts compare long COVID to. Researchers and medical professionals still don’t know exactly how COVID-19 causes those symptoms. But there are some theories.
 

Potential causes of long-COVID symptoms

Dr. Putrino said it is possible the virus enters a patient’s cells and hijacks the mitochondria – a part of the cell that provides energy. It can linger there for weeks or months – something known as viral persistence.

“All of a sudden, the body’s getting less energy for itself, even though it’s producing the same amount, or even a little more,” he said. And there is a consequence to this extra stress on the cells. “Creating energy isn’t free. You’re producing more waste products, which puts your body in a state of oxidative stress,” Dr. Putrino said. Oxidative stress damages cells as molecules interact with oxygen in harmful ways.

“The other big mechanism is autonomic dysfunction,” Dr. Putrino said. It’s marked by breathing problems, heart palpitations, and other glitches in areas most healthy people never have to think about. About 70% of long-COVID patients at Mount Sinai’s clinic have some degree of autonomic dysfunction, he said.

For a person with autonomic dysfunction, something as basic as changing posture can trigger a storm of cytokines, a chemical messenger that tells the immune system where and how to respond to challenges like an injury or infection.

“Suddenly, you have this on-off switch,” Dr. Putrino said. “You go straight to ‘fight or flight,’ ” with a surge of adrenaline and a spiking heart rate, “then plunge back to ‘rest or digest.’ You go from fired up to so sleepy, you can’t keep your eyes open.”

A patient with viral persistence and one with autonomic dysfunction may have the same negative reaction to exercise, even though the triggers are completely different.
 

So how can doctors help long-COVID patients?

The first step, Dr. Putrino said, is to understand the difference between long COVID and a long recovery from COVID-19 infection.

Many of the patients in the latter group still have symptoms 4 weeks after their first infection. “At 4 weeks, yeah, they’re still feeling symptoms, but that’s not long COVID,” he said. “That’s just taking a while to get over a viral infection.”

Fitness advice is simple for those people: Take it easy at first, and gradually increase the amount and intensity of aerobic exercise and strength training.

But that advice would be disastrous for someone who meets Dr. Putrino’s stricter definition of long COVID: “Three to 4 months out from initial infection, they’re experiencing severe fatigue, exertional symptoms, cognitive symptoms, heart palpitations, shortness of breath,” he said.

“Our clinic is extraordinarily cautious with exercise” for those patients, he said.

In Dr. Putrino’s experience, about 20%-30% of patients will make significant progress after 12 weeks. “They’re feeling more or less like they felt pre-COVID,” he said.

The unluckiest 10%-20% won’t make any progress at all. Any type of therapy, even if it’s as simple as moving their legs from a flat position, worsens their symptoms.

The majority – 50%-60% – will have some improvement in their symptoms. But then progress will stop, for reasons researchers are still trying to figure out.

“My sense is that gradually increasing your exercise is still good advice for the vast majority of people,” UCSF’s Dr. Durstenfeld said.

Ideally, that exercise will be supervised by someone trained in cardiac, pulmonary, and/or autonomic rehabilitation – a specialized type of therapy aimed at resyncing the autonomic nervous system that governs breathing and other unconscious functions, he said. But those therapies are rarely covered by insurance, which means most long-COVID patients are on their own.

Dr. Durstenfeld said it’s important that patients keep trying and not give up. “With slow and steady progress, a lot of people can get profoundly better,” he said.

Mr. Fram, who’s worked with careful supervision, says he’s getting closer to something like his pre-COVID-19 life.

But he’s not there yet. Long COVID, he said, “affects my life every single day.”

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

When Joel Fram woke up on the morning of March 12, 2020, he had a pretty good idea why he felt so lousy.

He lives in New York, where the first wave of the coronavirus was tearing through the city. “I instantly knew,” said the 55-year-old Broadway music director. It was COVID-19.

What started with a general sense of having been hit by a truck soon included a sore throat and such severe fatigue that he once fell asleep in the middle of sending a text to his sister. The final symptoms were chest tightness and trouble breathing.

And then he started to feel better. “By mid-April, my body was feeling essentially back to normal,” he said.

So he did what would have been smart after almost any other illness: He began working out. That didn’t last long. “It felt like someone pulled the carpet out from under me,” he remembered. “I couldn’t walk three blocks without getting breathless and fatigued.”

That was the first indication Mr. Fram had long COVID.

According to the National Center for Health Statistics, at least 7.5% of American adults – close to 20 million people – have symptoms of long COVID. And for almost all of those people, a growing body of evidence shows that exercise will make their symptoms worse.

COVID-19 patients who had the most severe illness will struggle the most with exercise later, according to a review published in June from researchers at the University of California, San Francisco. But even people with mild symptoms can struggle to regain their previous levels of fitness.

“We have participants in our study who had relatively mild acute symptoms and went on to have really profound decreases in their ability to exercise,” said Matthew S. Durstenfeld, MD, a cardiologist at UCSF and principal author of the review.

Most people with long COVID will have lower-than-expected scores on tests of aerobic fitness, as shown by Yale researchers in a study published in August 2021.

“Some amount of that is due to deconditioning,” Dr. Durstenfeld said. “You’re not feeling well, so you’re not exercising to the same degree you might have been before you got infected.”

In a study published in April, people with long COVID told researchers at Britain’s University of Leeds they spent 93% less time in physical activity than they did before their infection.

But multiple studies have found deconditioning is not entirely – or even mostly – to blame.

A 2021 study found that 89% of participants with long COVID had postexertional malaise (PEM), which happens when a patient’s symptoms get worse after they do even minor physical or mental activities. According to the CDC, postexertional malaise can hit as long as 12-48 hours after the activity, and it can take people up to 2 weeks to fully recover.

Unfortunately, the advice patients get from their doctors sometimes makes the problem worse.
 

How long COVID defies simple solutions

Long COVID is a “dynamic disability” that requires health professionals to go off script when a patient’s symptoms don’t respond in a predictable way to treatment, said David Putrino, PhD, a neuroscientist, physical therapist, and director of rehabilitation innovation for the Mount Sinai Health System in New York.

“We’re not so good at dealing with somebody who, for all intents and purposes, can appear healthy and nondisabled on one day and be completely debilitated the next day,” he said.

Dr. Putrino said more than half of his clinic’s long-COVID patients told his team they had at least one of these persistent problems:

• Fatigue (82%).
• Brain fog (67%).
• Headache (60%).
• Sleep problems (59%).
• Dizziness (54%).

And 86% said exercise worsened their symptoms.

The symptoms are similar to what doctors see with illnesses such as lupus, Lyme disease, and chronic fatigue syndrome – something many experts compare long COVID to. Researchers and medical professionals still don’t know exactly how COVID-19 causes those symptoms. But there are some theories.
 

Potential causes of long-COVID symptoms

Dr. Putrino said it is possible the virus enters a patient’s cells and hijacks the mitochondria – a part of the cell that provides energy. It can linger there for weeks or months – something known as viral persistence.

“All of a sudden, the body’s getting less energy for itself, even though it’s producing the same amount, or even a little more,” he said. And there is a consequence to this extra stress on the cells. “Creating energy isn’t free. You’re producing more waste products, which puts your body in a state of oxidative stress,” Dr. Putrino said. Oxidative stress damages cells as molecules interact with oxygen in harmful ways.

“The other big mechanism is autonomic dysfunction,” Dr. Putrino said. It’s marked by breathing problems, heart palpitations, and other glitches in areas most healthy people never have to think about. About 70% of long-COVID patients at Mount Sinai’s clinic have some degree of autonomic dysfunction, he said.

For a person with autonomic dysfunction, something as basic as changing posture can trigger a storm of cytokines, a chemical messenger that tells the immune system where and how to respond to challenges like an injury or infection.

“Suddenly, you have this on-off switch,” Dr. Putrino said. “You go straight to ‘fight or flight,’ ” with a surge of adrenaline and a spiking heart rate, “then plunge back to ‘rest or digest.’ You go from fired up to so sleepy, you can’t keep your eyes open.”

A patient with viral persistence and one with autonomic dysfunction may have the same negative reaction to exercise, even though the triggers are completely different.
 

So how can doctors help long-COVID patients?

The first step, Dr. Putrino said, is to understand the difference between long COVID and a long recovery from COVID-19 infection.

Many of the patients in the latter group still have symptoms 4 weeks after their first infection. “At 4 weeks, yeah, they’re still feeling symptoms, but that’s not long COVID,” he said. “That’s just taking a while to get over a viral infection.”

Fitness advice is simple for those people: Take it easy at first, and gradually increase the amount and intensity of aerobic exercise and strength training.

But that advice would be disastrous for someone who meets Dr. Putrino’s stricter definition of long COVID: “Three to 4 months out from initial infection, they’re experiencing severe fatigue, exertional symptoms, cognitive symptoms, heart palpitations, shortness of breath,” he said.

“Our clinic is extraordinarily cautious with exercise” for those patients, he said.

In Dr. Putrino’s experience, about 20%-30% of patients will make significant progress after 12 weeks. “They’re feeling more or less like they felt pre-COVID,” he said.

The unluckiest 10%-20% won’t make any progress at all. Any type of therapy, even if it’s as simple as moving their legs from a flat position, worsens their symptoms.

The majority – 50%-60% – will have some improvement in their symptoms. But then progress will stop, for reasons researchers are still trying to figure out.

“My sense is that gradually increasing your exercise is still good advice for the vast majority of people,” UCSF’s Dr. Durstenfeld said.

Ideally, that exercise will be supervised by someone trained in cardiac, pulmonary, and/or autonomic rehabilitation – a specialized type of therapy aimed at resyncing the autonomic nervous system that governs breathing and other unconscious functions, he said. But those therapies are rarely covered by insurance, which means most long-COVID patients are on their own.

Dr. Durstenfeld said it’s important that patients keep trying and not give up. “With slow and steady progress, a lot of people can get profoundly better,” he said.

Mr. Fram, who’s worked with careful supervision, says he’s getting closer to something like his pre-COVID-19 life.

But he’s not there yet. Long COVID, he said, “affects my life every single day.”

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

When Joel Fram woke up on the morning of March 12, 2020, he had a pretty good idea why he felt so lousy.

He lives in New York, where the first wave of the coronavirus was tearing through the city. “I instantly knew,” said the 55-year-old Broadway music director. It was COVID-19.

What started with a general sense of having been hit by a truck soon included a sore throat and such severe fatigue that he once fell asleep in the middle of sending a text to his sister. The final symptoms were chest tightness and trouble breathing.

And then he started to feel better. “By mid-April, my body was feeling essentially back to normal,” he said.

So he did what would have been smart after almost any other illness: He began working out. That didn’t last long. “It felt like someone pulled the carpet out from under me,” he remembered. “I couldn’t walk three blocks without getting breathless and fatigued.”

That was the first indication Mr. Fram had long COVID.

According to the National Center for Health Statistics, at least 7.5% of American adults – close to 20 million people – have symptoms of long COVID. And for almost all of those people, a growing body of evidence shows that exercise will make their symptoms worse.

COVID-19 patients who had the most severe illness will struggle the most with exercise later, according to a review published in June from researchers at the University of California, San Francisco. But even people with mild symptoms can struggle to regain their previous levels of fitness.

“We have participants in our study who had relatively mild acute symptoms and went on to have really profound decreases in their ability to exercise,” said Matthew S. Durstenfeld, MD, a cardiologist at UCSF and principal author of the review.

Most people with long COVID will have lower-than-expected scores on tests of aerobic fitness, as shown by Yale researchers in a study published in August 2021.

“Some amount of that is due to deconditioning,” Dr. Durstenfeld said. “You’re not feeling well, so you’re not exercising to the same degree you might have been before you got infected.”

In a study published in April, people with long COVID told researchers at Britain’s University of Leeds they spent 93% less time in physical activity than they did before their infection.

But multiple studies have found deconditioning is not entirely – or even mostly – to blame.

A 2021 study found that 89% of participants with long COVID had postexertional malaise (PEM), which happens when a patient’s symptoms get worse after they do even minor physical or mental activities. According to the CDC, postexertional malaise can hit as long as 12-48 hours after the activity, and it can take people up to 2 weeks to fully recover.

Unfortunately, the advice patients get from their doctors sometimes makes the problem worse.
 

How long COVID defies simple solutions

Long COVID is a “dynamic disability” that requires health professionals to go off script when a patient’s symptoms don’t respond in a predictable way to treatment, said David Putrino, PhD, a neuroscientist, physical therapist, and director of rehabilitation innovation for the Mount Sinai Health System in New York.

“We’re not so good at dealing with somebody who, for all intents and purposes, can appear healthy and nondisabled on one day and be completely debilitated the next day,” he said.

Dr. Putrino said more than half of his clinic’s long-COVID patients told his team they had at least one of these persistent problems:

• Fatigue (82%).
• Brain fog (67%).
• Headache (60%).
• Sleep problems (59%).
• Dizziness (54%).

And 86% said exercise worsened their symptoms.

The symptoms are similar to what doctors see with illnesses such as lupus, Lyme disease, and chronic fatigue syndrome – something many experts compare long COVID to. Researchers and medical professionals still don’t know exactly how COVID-19 causes those symptoms. But there are some theories.
 

Potential causes of long-COVID symptoms

Dr. Putrino said it is possible the virus enters a patient’s cells and hijacks the mitochondria – a part of the cell that provides energy. It can linger there for weeks or months – something known as viral persistence.

“All of a sudden, the body’s getting less energy for itself, even though it’s producing the same amount, or even a little more,” he said. And there is a consequence to this extra stress on the cells. “Creating energy isn’t free. You’re producing more waste products, which puts your body in a state of oxidative stress,” Dr. Putrino said. Oxidative stress damages cells as molecules interact with oxygen in harmful ways.

“The other big mechanism is autonomic dysfunction,” Dr. Putrino said. It’s marked by breathing problems, heart palpitations, and other glitches in areas most healthy people never have to think about. About 70% of long-COVID patients at Mount Sinai’s clinic have some degree of autonomic dysfunction, he said.

For a person with autonomic dysfunction, something as basic as changing posture can trigger a storm of cytokines, a chemical messenger that tells the immune system where and how to respond to challenges like an injury or infection.

“Suddenly, you have this on-off switch,” Dr. Putrino said. “You go straight to ‘fight or flight,’ ” with a surge of adrenaline and a spiking heart rate, “then plunge back to ‘rest or digest.’ You go from fired up to so sleepy, you can’t keep your eyes open.”

A patient with viral persistence and one with autonomic dysfunction may have the same negative reaction to exercise, even though the triggers are completely different.
 

So how can doctors help long-COVID patients?

The first step, Dr. Putrino said, is to understand the difference between long COVID and a long recovery from COVID-19 infection.

Many of the patients in the latter group still have symptoms 4 weeks after their first infection. “At 4 weeks, yeah, they’re still feeling symptoms, but that’s not long COVID,” he said. “That’s just taking a while to get over a viral infection.”

Fitness advice is simple for those people: Take it easy at first, and gradually increase the amount and intensity of aerobic exercise and strength training.

But that advice would be disastrous for someone who meets Dr. Putrino’s stricter definition of long COVID: “Three to 4 months out from initial infection, they’re experiencing severe fatigue, exertional symptoms, cognitive symptoms, heart palpitations, shortness of breath,” he said.

“Our clinic is extraordinarily cautious with exercise” for those patients, he said.

In Dr. Putrino’s experience, about 20%-30% of patients will make significant progress after 12 weeks. “They’re feeling more or less like they felt pre-COVID,” he said.

The unluckiest 10%-20% won’t make any progress at all. Any type of therapy, even if it’s as simple as moving their legs from a flat position, worsens their symptoms.

The majority – 50%-60% – will have some improvement in their symptoms. But then progress will stop, for reasons researchers are still trying to figure out.

“My sense is that gradually increasing your exercise is still good advice for the vast majority of people,” UCSF’s Dr. Durstenfeld said.

Ideally, that exercise will be supervised by someone trained in cardiac, pulmonary, and/or autonomic rehabilitation – a specialized type of therapy aimed at resyncing the autonomic nervous system that governs breathing and other unconscious functions, he said. But those therapies are rarely covered by insurance, which means most long-COVID patients are on their own.

Dr. Durstenfeld said it’s important that patients keep trying and not give up. “With slow and steady progress, a lot of people can get profoundly better,” he said.

Mr. Fram, who’s worked with careful supervision, says he’s getting closer to something like his pre-COVID-19 life.

But he’s not there yet. Long COVID, he said, “affects my life every single day.”

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

We tend to think a good night’s sleep should be uninterrupted, but surprising new research from the University of Copenhagen suggests just the opposite: Brief awakenings may be a sign you’ve slept well.

The study, done on mice, found that the stress transmitter noradrenaline wakes up the brain many times a night. These “microarousals” were linked to memory consolidation, meaning they help you remember the previous day’s events. In fact, the more “awake” you are during a microarousal, the better the memory boost, suggests the research, which was published in Nature Neuroscience.

“Every time I wake up in the middle of the night now, I think – ah, nice, I probably just had great memory-boosting sleep,” said study author Celia Kjaerby, PhD, an assistant professor at the university’s Center for Translational Neuromedicine.

The findings add insight to what happens in the brain during sleep and may help pave the way for new treatments for those who have sleep disorders.
 

Waves of noradrenaline

Previous research has suggested that noradrenaline – a hormone that increases during stress but also helps you stay focused – is inactive during sleep. So, the researchers were surprised to see high levels of it in the brains of the sleeping rodents.

“I still remember seeing the first traces showing the brain activity of the norepinephrine stress system during sleep. We could not believe our eyes,” Dr. Kjaerby said. “Everyone had thought the system would be quiet. And now we have found out that it completely controls the microarchitecture of sleep.”

Those noradrenaline levels rise and fall like waves every 30 seconds during non-REM (NREM) sleep. At each “peak” the brain is briefly awake, and at each “valley” it is asleep. Typically, these awakenings are so brief that the sleeping subject does not notice. But the higher the rise, the longer the awakening – and the more likely the sleeper may notice.

During the valleys, or when norepinephrine drops, so-called sleep spindles occur.

“These are short oscillatory bursts of brain activity linked to memory consolidation,” Dr. Kjaerby said. Occasionally there is a “deep valley,” lasting 3-5 minutes, leading to more sleep spindles. The mice with the most deep valleys also had the best memories, the researchers noted.

“We have shown that the amount of these super-boosts of sleep spindles, and not REM sleep, defines how well you remember the experiences you had prior to going to sleep,” said Dr. Kjaerby.

Deep valleys were followed by longer awakenings, the researchers observed. So, the longer the valley, the longer the awakening – and the better the memory boost. This means that, though restless sleep is not good, waking up briefly may be a natural part of memory-related sleep phases and may even mean you’ve slept well.
 

What happens in our brains when we sleep: Piecing it together

The findings fit with previous clinical data that shows we wake up roughly 100-plus times a night, mostly during NREM sleep stage 2 (the spindle-rich sleep stage), Dr. Kjaerby said.

Still, more research on these small awakenings is needed, Dr. Kjaerby said, noting that professor Maiken Nedergaard, MD, another author of this study, has found that the brain cleans up waste products through a rinsing fluid system.

“It remains a puzzle why the fluid system is so active when we sleep,” Dr. Kjaerby said. “We believe these short awakenings could potentially be the key to answering this question.”

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

We tend to think a good night’s sleep should be uninterrupted, but surprising new research from the University of Copenhagen suggests just the opposite: Brief awakenings may be a sign you’ve slept well.

The study, done on mice, found that the stress transmitter noradrenaline wakes up the brain many times a night. These “microarousals” were linked to memory consolidation, meaning they help you remember the previous day’s events. In fact, the more “awake” you are during a microarousal, the better the memory boost, suggests the research, which was published in Nature Neuroscience.

“Every time I wake up in the middle of the night now, I think – ah, nice, I probably just had great memory-boosting sleep,” said study author Celia Kjaerby, PhD, an assistant professor at the university’s Center for Translational Neuromedicine.

The findings add insight to what happens in the brain during sleep and may help pave the way for new treatments for those who have sleep disorders.
 

Waves of noradrenaline

Previous research has suggested that noradrenaline – a hormone that increases during stress but also helps you stay focused – is inactive during sleep. So, the researchers were surprised to see high levels of it in the brains of the sleeping rodents.

“I still remember seeing the first traces showing the brain activity of the norepinephrine stress system during sleep. We could not believe our eyes,” Dr. Kjaerby said. “Everyone had thought the system would be quiet. And now we have found out that it completely controls the microarchitecture of sleep.”

Those noradrenaline levels rise and fall like waves every 30 seconds during non-REM (NREM) sleep. At each “peak” the brain is briefly awake, and at each “valley” it is asleep. Typically, these awakenings are so brief that the sleeping subject does not notice. But the higher the rise, the longer the awakening – and the more likely the sleeper may notice.

During the valleys, or when norepinephrine drops, so-called sleep spindles occur.

“These are short oscillatory bursts of brain activity linked to memory consolidation,” Dr. Kjaerby said. Occasionally there is a “deep valley,” lasting 3-5 minutes, leading to more sleep spindles. The mice with the most deep valleys also had the best memories, the researchers noted.

“We have shown that the amount of these super-boosts of sleep spindles, and not REM sleep, defines how well you remember the experiences you had prior to going to sleep,” said Dr. Kjaerby.

Deep valleys were followed by longer awakenings, the researchers observed. So, the longer the valley, the longer the awakening – and the better the memory boost. This means that, though restless sleep is not good, waking up briefly may be a natural part of memory-related sleep phases and may even mean you’ve slept well.
 

What happens in our brains when we sleep: Piecing it together

The findings fit with previous clinical data that shows we wake up roughly 100-plus times a night, mostly during NREM sleep stage 2 (the spindle-rich sleep stage), Dr. Kjaerby said.

Still, more research on these small awakenings is needed, Dr. Kjaerby said, noting that professor Maiken Nedergaard, MD, another author of this study, has found that the brain cleans up waste products through a rinsing fluid system.

“It remains a puzzle why the fluid system is so active when we sleep,” Dr. Kjaerby said. “We believe these short awakenings could potentially be the key to answering this question.”

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

We tend to think a good night’s sleep should be uninterrupted, but surprising new research from the University of Copenhagen suggests just the opposite: Brief awakenings may be a sign you’ve slept well.

The study, done on mice, found that the stress transmitter noradrenaline wakes up the brain many times a night. These “microarousals” were linked to memory consolidation, meaning they help you remember the previous day’s events. In fact, the more “awake” you are during a microarousal, the better the memory boost, suggests the research, which was published in Nature Neuroscience.

“Every time I wake up in the middle of the night now, I think – ah, nice, I probably just had great memory-boosting sleep,” said study author Celia Kjaerby, PhD, an assistant professor at the university’s Center for Translational Neuromedicine.

The findings add insight to what happens in the brain during sleep and may help pave the way for new treatments for those who have sleep disorders.
 

Waves of noradrenaline

Previous research has suggested that noradrenaline – a hormone that increases during stress but also helps you stay focused – is inactive during sleep. So, the researchers were surprised to see high levels of it in the brains of the sleeping rodents.

“I still remember seeing the first traces showing the brain activity of the norepinephrine stress system during sleep. We could not believe our eyes,” Dr. Kjaerby said. “Everyone had thought the system would be quiet. And now we have found out that it completely controls the microarchitecture of sleep.”

Those noradrenaline levels rise and fall like waves every 30 seconds during non-REM (NREM) sleep. At each “peak” the brain is briefly awake, and at each “valley” it is asleep. Typically, these awakenings are so brief that the sleeping subject does not notice. But the higher the rise, the longer the awakening – and the more likely the sleeper may notice.

During the valleys, or when norepinephrine drops, so-called sleep spindles occur.

“These are short oscillatory bursts of brain activity linked to memory consolidation,” Dr. Kjaerby said. Occasionally there is a “deep valley,” lasting 3-5 minutes, leading to more sleep spindles. The mice with the most deep valleys also had the best memories, the researchers noted.

“We have shown that the amount of these super-boosts of sleep spindles, and not REM sleep, defines how well you remember the experiences you had prior to going to sleep,” said Dr. Kjaerby.

Deep valleys were followed by longer awakenings, the researchers observed. So, the longer the valley, the longer the awakening – and the better the memory boost. This means that, though restless sleep is not good, waking up briefly may be a natural part of memory-related sleep phases and may even mean you’ve slept well.
 

What happens in our brains when we sleep: Piecing it together

The findings fit with previous clinical data that shows we wake up roughly 100-plus times a night, mostly during NREM sleep stage 2 (the spindle-rich sleep stage), Dr. Kjaerby said.

Still, more research on these small awakenings is needed, Dr. Kjaerby said, noting that professor Maiken Nedergaard, MD, another author of this study, has found that the brain cleans up waste products through a rinsing fluid system.

“It remains a puzzle why the fluid system is so active when we sleep,” Dr. Kjaerby said. “We believe these short awakenings could potentially be the key to answering this question.”

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

Consistently earning a low salary in midlife is associated with increased memory decline in older age, new research suggests. In a new analysis of more than 3,000 participants in the Health and Retirement Study, those who sustained low wages in midlife showed significantly faster memory decline than their peers who never earned low wages.

The findings could have implications for future public policy and research initiatives, the investigators noted.

“Our findings, which suggest a pattern of sustained low-wage earning is harmful for cognitive health, [are] broadly applicable to researchers across numerous health disciplines,” said co-investigator Katrina Kezios, PhD, postdoctoral researcher, department of epidemiology, Mailman School of Public Health, Columbia University, New York.

The findings were presented at the 2022 Alzheimer’s Association International Conference.
 

Growing number of low-wage workers

Low-wage workers make up a growing share of the U.S. labor market. Yet little research has examined the long-term relationship between earning low wages and memory decline.

The current investigators assessed 1992-2016 data from the Health and Retirement Study, a longitudinal survey of nationally representative samples of Americans aged 50 years and older. Study participants are interviewed every 2 years and provide, among other things, information on work-related factors, including hourly wages.

Memory function was measured at each visit from 2004 to 2016 using a memory composite score. The score included immediate and delayed word recall memory assessments. For those who became too impaired to complete cognitive assessment, memory tests by proxy informants were utilized.

On average, participants completed 4.8 memory assessments over the course of the study.

Researchers defined “low wage” as an hourly wage lower than two-thirds of the federal median wage for the corresponding year. They categorized low-wage exposure history as “never” or “intermittent” or “sustained” on the basis of wages earned from 1992 to 2004.

The current analysis included 3,803 participants, 1,913 of whom were men. All participants were born from 1936 to 1941. In 2004, the average age was 65 years, and the mean memory score was 1.15 standard units.

The investigators adjusted for factors that could confound the relationship between wages and cognition, including the participant’s education, parental education, household wealth, and marital status. Later, whether the participants’ occupation type was of low skill or not was also included.
 

Cognitive harm

The confounder-adjusted annual rate of memory decline among workers who never earned low wages was –0.12 standard units (95% confidence interval, –0.14 to –0.10).

Compared with these workers, memory decline was significantly faster among participants with sustained low wage–earning during midlife (beta for interaction between time and exposure group, –0.012; 95% CI, –0.02 to 0.01), corresponding to an annual rate of –0.13 standard units.

Put another way, the cognitive aging experienced by workers earning low wages over a 10-year period was equivalent to what workers who never earned low wages would experience over 11 years.

Although similar associations were found for men and women, it was stronger in magnitude for men – a finding Dr. Kezios said was somewhat surprising. She noted that women are commonly more at risk for dementia than men.

However, she advises caution in interpreting this finding, as there were so few men in the sustained low-wage group. “Women disproportionately make up the group of workers earning low wages,” she said.

The negative low coefficient found for those who persistently earned low wages was also observed for those who intermittently earned low wages, but this was not statistically significant.

“We can speculate or hypothesize the cumulative effect of earning low wages at each exposure interval produces more cognitive harm than maybe earning low wages at some time points over that exposure period,” said Dr. Kezios.

A sensitivity analysis that examined wage earning at the same ages but in two different birth cohorts showed similar results for the two groups. When researchers removed self-employed workers from the study sample, the same association between sustained low wages and memory decline was found.

“Our findings held up, which gave us a little more reassurance that what we were seeing is at least signaling there might be something there,” said Dr. Kezios.

She described the study as a “first pass” for documenting the harmful cognitive effects of consistently earning low wages.

It would be interesting, she said, to now determine whether there’s a “dose effect” for having a low salary. However, other studies with different designs would be needed to determine at what income level cognitive health starts to be protected and the impact of raising the minimum wage, she added.
 

Unique study

Heather Snyder, PhD, vice president of medical and scientific relations, Alzheimer’s Association, said the study was unique. “I don’t think we have seen anything like this before,” said Dr. Snyder.

The study, which links sustained low-wage earning in midlife to later memory decline, “is looking beyond some of the other measures we’ve seen when we looked at socioeconomic status,” she noted.

The results “beg the question” of whether people who earn low wages have less access to health care, she added.

“We should think about how to ensure access and equity around health care and around potential ways that may address components of risk individuals have during their life course,” Dr. Snyder said.

She noted that the study provides a “start” at considering potential policies to address the impact of sustained low wages on overall health, particularly cognitive health, throughout life.

The study had no outside funding. Dr. Kezios has reported no relevant financial relationships.

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

Consistently earning a low salary in midlife is associated with increased memory decline in older age, new research suggests. In a new analysis of more than 3,000 participants in the Health and Retirement Study, those who sustained low wages in midlife showed significantly faster memory decline than their peers who never earned low wages.

The findings could have implications for future public policy and research initiatives, the investigators noted.

“Our findings, which suggest a pattern of sustained low-wage earning is harmful for cognitive health, [are] broadly applicable to researchers across numerous health disciplines,” said co-investigator Katrina Kezios, PhD, postdoctoral researcher, department of epidemiology, Mailman School of Public Health, Columbia University, New York.

The findings were presented at the 2022 Alzheimer’s Association International Conference.
 

Growing number of low-wage workers

Low-wage workers make up a growing share of the U.S. labor market. Yet little research has examined the long-term relationship between earning low wages and memory decline.

The current investigators assessed 1992-2016 data from the Health and Retirement Study, a longitudinal survey of nationally representative samples of Americans aged 50 years and older. Study participants are interviewed every 2 years and provide, among other things, information on work-related factors, including hourly wages.

Memory function was measured at each visit from 2004 to 2016 using a memory composite score. The score included immediate and delayed word recall memory assessments. For those who became too impaired to complete cognitive assessment, memory tests by proxy informants were utilized.

On average, participants completed 4.8 memory assessments over the course of the study.

Researchers defined “low wage” as an hourly wage lower than two-thirds of the federal median wage for the corresponding year. They categorized low-wage exposure history as “never” or “intermittent” or “sustained” on the basis of wages earned from 1992 to 2004.

The current analysis included 3,803 participants, 1,913 of whom were men. All participants were born from 1936 to 1941. In 2004, the average age was 65 years, and the mean memory score was 1.15 standard units.

The investigators adjusted for factors that could confound the relationship between wages and cognition, including the participant’s education, parental education, household wealth, and marital status. Later, whether the participants’ occupation type was of low skill or not was also included.
 

Cognitive harm

The confounder-adjusted annual rate of memory decline among workers who never earned low wages was –0.12 standard units (95% confidence interval, –0.14 to –0.10).

Compared with these workers, memory decline was significantly faster among participants with sustained low wage–earning during midlife (beta for interaction between time and exposure group, –0.012; 95% CI, –0.02 to 0.01), corresponding to an annual rate of –0.13 standard units.

Put another way, the cognitive aging experienced by workers earning low wages over a 10-year period was equivalent to what workers who never earned low wages would experience over 11 years.

Although similar associations were found for men and women, it was stronger in magnitude for men – a finding Dr. Kezios said was somewhat surprising. She noted that women are commonly more at risk for dementia than men.

However, she advises caution in interpreting this finding, as there were so few men in the sustained low-wage group. “Women disproportionately make up the group of workers earning low wages,” she said.

The negative low coefficient found for those who persistently earned low wages was also observed for those who intermittently earned low wages, but this was not statistically significant.

“We can speculate or hypothesize the cumulative effect of earning low wages at each exposure interval produces more cognitive harm than maybe earning low wages at some time points over that exposure period,” said Dr. Kezios.

A sensitivity analysis that examined wage earning at the same ages but in two different birth cohorts showed similar results for the two groups. When researchers removed self-employed workers from the study sample, the same association between sustained low wages and memory decline was found.

“Our findings held up, which gave us a little more reassurance that what we were seeing is at least signaling there might be something there,” said Dr. Kezios.

She described the study as a “first pass” for documenting the harmful cognitive effects of consistently earning low wages.

It would be interesting, she said, to now determine whether there’s a “dose effect” for having a low salary. However, other studies with different designs would be needed to determine at what income level cognitive health starts to be protected and the impact of raising the minimum wage, she added.
 

Unique study

Heather Snyder, PhD, vice president of medical and scientific relations, Alzheimer’s Association, said the study was unique. “I don’t think we have seen anything like this before,” said Dr. Snyder.

The study, which links sustained low-wage earning in midlife to later memory decline, “is looking beyond some of the other measures we’ve seen when we looked at socioeconomic status,” she noted.

The results “beg the question” of whether people who earn low wages have less access to health care, she added.

“We should think about how to ensure access and equity around health care and around potential ways that may address components of risk individuals have during their life course,” Dr. Snyder said.

She noted that the study provides a “start” at considering potential policies to address the impact of sustained low wages on overall health, particularly cognitive health, throughout life.

The study had no outside funding. Dr. Kezios has reported no relevant financial relationships.

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

Consistently earning a low salary in midlife is associated with increased memory decline in older age, new research suggests. In a new analysis of more than 3,000 participants in the Health and Retirement Study, those who sustained low wages in midlife showed significantly faster memory decline than their peers who never earned low wages.

The findings could have implications for future public policy and research initiatives, the investigators noted.

“Our findings, which suggest a pattern of sustained low-wage earning is harmful for cognitive health, [are] broadly applicable to researchers across numerous health disciplines,” said co-investigator Katrina Kezios, PhD, postdoctoral researcher, department of epidemiology, Mailman School of Public Health, Columbia University, New York.

The findings were presented at the 2022 Alzheimer’s Association International Conference.
 

Growing number of low-wage workers

Low-wage workers make up a growing share of the U.S. labor market. Yet little research has examined the long-term relationship between earning low wages and memory decline.

The current investigators assessed 1992-2016 data from the Health and Retirement Study, a longitudinal survey of nationally representative samples of Americans aged 50 years and older. Study participants are interviewed every 2 years and provide, among other things, information on work-related factors, including hourly wages.

Memory function was measured at each visit from 2004 to 2016 using a memory composite score. The score included immediate and delayed word recall memory assessments. For those who became too impaired to complete cognitive assessment, memory tests by proxy informants were utilized.

On average, participants completed 4.8 memory assessments over the course of the study.

Researchers defined “low wage” as an hourly wage lower than two-thirds of the federal median wage for the corresponding year. They categorized low-wage exposure history as “never” or “intermittent” or “sustained” on the basis of wages earned from 1992 to 2004.

The current analysis included 3,803 participants, 1,913 of whom were men. All participants were born from 1936 to 1941. In 2004, the average age was 65 years, and the mean memory score was 1.15 standard units.

The investigators adjusted for factors that could confound the relationship between wages and cognition, including the participant’s education, parental education, household wealth, and marital status. Later, whether the participants’ occupation type was of low skill or not was also included.
 

Cognitive harm

The confounder-adjusted annual rate of memory decline among workers who never earned low wages was –0.12 standard units (95% confidence interval, –0.14 to –0.10).

Compared with these workers, memory decline was significantly faster among participants with sustained low wage–earning during midlife (beta for interaction between time and exposure group, –0.012; 95% CI, –0.02 to 0.01), corresponding to an annual rate of –0.13 standard units.

Put another way, the cognitive aging experienced by workers earning low wages over a 10-year period was equivalent to what workers who never earned low wages would experience over 11 years.

Although similar associations were found for men and women, it was stronger in magnitude for men – a finding Dr. Kezios said was somewhat surprising. She noted that women are commonly more at risk for dementia than men.

However, she advises caution in interpreting this finding, as there were so few men in the sustained low-wage group. “Women disproportionately make up the group of workers earning low wages,” she said.

The negative low coefficient found for those who persistently earned low wages was also observed for those who intermittently earned low wages, but this was not statistically significant.

“We can speculate or hypothesize the cumulative effect of earning low wages at each exposure interval produces more cognitive harm than maybe earning low wages at some time points over that exposure period,” said Dr. Kezios.

A sensitivity analysis that examined wage earning at the same ages but in two different birth cohorts showed similar results for the two groups. When researchers removed self-employed workers from the study sample, the same association between sustained low wages and memory decline was found.

“Our findings held up, which gave us a little more reassurance that what we were seeing is at least signaling there might be something there,” said Dr. Kezios.

She described the study as a “first pass” for documenting the harmful cognitive effects of consistently earning low wages.

It would be interesting, she said, to now determine whether there’s a “dose effect” for having a low salary. However, other studies with different designs would be needed to determine at what income level cognitive health starts to be protected and the impact of raising the minimum wage, she added.
 

Unique study

Heather Snyder, PhD, vice president of medical and scientific relations, Alzheimer’s Association, said the study was unique. “I don’t think we have seen anything like this before,” said Dr. Snyder.

The study, which links sustained low-wage earning in midlife to later memory decline, “is looking beyond some of the other measures we’ve seen when we looked at socioeconomic status,” she noted.

The results “beg the question” of whether people who earn low wages have less access to health care, she added.

“We should think about how to ensure access and equity around health care and around potential ways that may address components of risk individuals have during their life course,” Dr. Snyder said.

She noted that the study provides a “start” at considering potential policies to address the impact of sustained low wages on overall health, particularly cognitive health, throughout life.

The study had no outside funding. Dr. Kezios has reported no relevant financial relationships.

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

Everyone gets by using environmental cues: For example, if you have to go to use the toilet in public, a bathroom sign prompts an immediate response. However, patients with dementia often struggle with environmental cues, which can complicate the already difficult task faced by their caregivers.

Individuals with dementia can lose awareness of such signs, and even colors, making it harder for them to interpret environmental cues.

A new pilot study showed that a telehealth intervention focusing on individualized treatment and environmental cues can be delivered to patients and caregivers in a rural environment.

The study, presented at the Alzheimer’s Association International Conference, recruited 30 pairs of patients and their caregivers. The approach is based on the Dunn model of sensory processing, which focuses on altering environments to maximize chances of success. It “explains that sensory processing is the information coming in, and then our ability to regulate and habituate to those sensations (creates) behavior,” Elizabeth Rhodus, MD, PhD, said during her talk. Dr. Rhodus is assistant professor of medicine at the University of Kentucky, Lexington.

Sensory-based interventions are not uncommon, but most are applied to pediatric populations and tend to focus on sensory processing disorders and autism spectrum disorder. The few programs that do focus on adults have varying methods and produce mixed results. Dr. Rhodus thinks that the key to success is individualization of therapy. “You’re going to like a certain sensation, and I might not like it. You can’t put us in the same room and expect the same results. We have to identify the preferences of how people interact with their environment, and what their brain does at a neuroscience level with that information,” she said.
 

Caregiving hacks

The program employs telehealth to work with caregivers so they can also create sensory environments within the home, using environment to trigger behavior.

For example, although individuals with dementia may have reduced response to color, the color red is unique. “Red is a cortical trigger. Red always stands out to people, so in our package that we send out as part of this intervention, we send out a roll of red duct tape,” said Dr. Rhodus.

An example of the use of red was a patient with dementia who had stopped drinking on his own, causing his caregiver daughter to be concerned that he would soon have to enter a nursing home. Examining the room, the occupational therapist realized that the water was kept out of sight, and suggested that the water glass be placed within the patient’s view, atop a square created with the red duct tape.

“These are just some of the simple concepts. They kind of seem easy. Some of my participants call them caregiving hacks, but it’s things that are grounded in neuroscience – how the brain processes the environment, and then how can we plug in supports and cues in whatever area is missing,” said Dr. Rhodus.

In the program, the caregiver fills out several online surveys, and an occupational therapist conducts an interview to identify specific challenges, such as bathing, or using the toilet, or going to church. Then an adult sensory profile reveals how the patient perceives his or her environment. “It’s taking those individual pieces, and then boiling it down to these mechanisms at the behavioral and neuroscience level,” said Dr. Rhodus. She said the entire setup process takes about an hour.
 

Impactful care

The individualized approach of the HARMONY (Helping Older Adults Create and Manage Occupations Successfully) method is promising, according to Monika Gross, executive director of the Poise Project, which uses the Alexander Technique to help people with chronic conditions such as Parkinson’s disease.

“Although it’s always a very simple idea that human beings need sensory processing aspects in their lives, from the time they’re infants through to the end of life, we don’t really focus on the end of life in a way that can bring meaning between the care partner and the person living with dementia. The other thing that was impressive is that this is in a rural community, where there often aren’t a lot of resources available, (such as) classes that the care partner can take their loved one to. So having something where the care partner has some confidence that they can really make an impact in that person that they are seeing decline, that they can see their behavior change [is good],” said Ms. Gross.
 

Empowering caregivers

The study included 30 pairs of patients and caregivers who were randomized to the individualized care (I), standardized care, or a control group. Adherence to weekly visits was high (I, 88%; S, 100%; C, 60%; P = .061). Retention was strong (I, 80%; S, 60%; C, 50%).

“It was feasible ... and at the end, we found a significant improvement in care partner satisfaction. We actually empowered these people to care for their loved ones, and in doing that, and helping them set up environmental cues, it allowed that person to perform at a more independent level,” said Dr. Rhodus.

The trial was only a proof of concept, so although the researchers saw signs of efficacy, it wasn’t powered to show that. They are currently enrolling additional patients and caregivers for larger studies to further test the approach.

Dr. Rhodus and Ms. Gross have no relevant financial disclosures.

Everyone gets by using environmental cues: For example, if you have to go to use the toilet in public, a bathroom sign prompts an immediate response. However, patients with dementia often struggle with environmental cues, which can complicate the already difficult task faced by their caregivers.

Individuals with dementia can lose awareness of such signs, and even colors, making it harder for them to interpret environmental cues.

A new pilot study showed that a telehealth intervention focusing on individualized treatment and environmental cues can be delivered to patients and caregivers in a rural environment.

The study, presented at the Alzheimer’s Association International Conference, recruited 30 pairs of patients and their caregivers. The approach is based on the Dunn model of sensory processing, which focuses on altering environments to maximize chances of success. It “explains that sensory processing is the information coming in, and then our ability to regulate and habituate to those sensations (creates) behavior,” Elizabeth Rhodus, MD, PhD, said during her talk. Dr. Rhodus is assistant professor of medicine at the University of Kentucky, Lexington.

Sensory-based interventions are not uncommon, but most are applied to pediatric populations and tend to focus on sensory processing disorders and autism spectrum disorder. The few programs that do focus on adults have varying methods and produce mixed results. Dr. Rhodus thinks that the key to success is individualization of therapy. “You’re going to like a certain sensation, and I might not like it. You can’t put us in the same room and expect the same results. We have to identify the preferences of how people interact with their environment, and what their brain does at a neuroscience level with that information,” she said.
 

Caregiving hacks

The program employs telehealth to work with caregivers so they can also create sensory environments within the home, using environment to trigger behavior.

For example, although individuals with dementia may have reduced response to color, the color red is unique. “Red is a cortical trigger. Red always stands out to people, so in our package that we send out as part of this intervention, we send out a roll of red duct tape,” said Dr. Rhodus.

An example of the use of red was a patient with dementia who had stopped drinking on his own, causing his caregiver daughter to be concerned that he would soon have to enter a nursing home. Examining the room, the occupational therapist realized that the water was kept out of sight, and suggested that the water glass be placed within the patient’s view, atop a square created with the red duct tape.

“These are just some of the simple concepts. They kind of seem easy. Some of my participants call them caregiving hacks, but it’s things that are grounded in neuroscience – how the brain processes the environment, and then how can we plug in supports and cues in whatever area is missing,” said Dr. Rhodus.

In the program, the caregiver fills out several online surveys, and an occupational therapist conducts an interview to identify specific challenges, such as bathing, or using the toilet, or going to church. Then an adult sensory profile reveals how the patient perceives his or her environment. “It’s taking those individual pieces, and then boiling it down to these mechanisms at the behavioral and neuroscience level,” said Dr. Rhodus. She said the entire setup process takes about an hour.
 

Impactful care

The individualized approach of the HARMONY (Helping Older Adults Create and Manage Occupations Successfully) method is promising, according to Monika Gross, executive director of the Poise Project, which uses the Alexander Technique to help people with chronic conditions such as Parkinson’s disease.

“Although it’s always a very simple idea that human beings need sensory processing aspects in their lives, from the time they’re infants through to the end of life, we don’t really focus on the end of life in a way that can bring meaning between the care partner and the person living with dementia. The other thing that was impressive is that this is in a rural community, where there often aren’t a lot of resources available, (such as) classes that the care partner can take their loved one to. So having something where the care partner has some confidence that they can really make an impact in that person that they are seeing decline, that they can see their behavior change [is good],” said Ms. Gross.
 

Empowering caregivers

The study included 30 pairs of patients and caregivers who were randomized to the individualized care (I), standardized care, or a control group. Adherence to weekly visits was high (I, 88%; S, 100%; C, 60%; P = .061). Retention was strong (I, 80%; S, 60%; C, 50%).

“It was feasible ... and at the end, we found a significant improvement in care partner satisfaction. We actually empowered these people to care for their loved ones, and in doing that, and helping them set up environmental cues, it allowed that person to perform at a more independent level,” said Dr. Rhodus.

The trial was only a proof of concept, so although the researchers saw signs of efficacy, it wasn’t powered to show that. They are currently enrolling additional patients and caregivers for larger studies to further test the approach.

Dr. Rhodus and Ms. Gross have no relevant financial disclosures.

Everyone gets by using environmental cues: For example, if you have to go to use the toilet in public, a bathroom sign prompts an immediate response. However, patients with dementia often struggle with environmental cues, which can complicate the already difficult task faced by their caregivers.

Individuals with dementia can lose awareness of such signs, and even colors, making it harder for them to interpret environmental cues.

A new pilot study showed that a telehealth intervention focusing on individualized treatment and environmental cues can be delivered to patients and caregivers in a rural environment.

The study, presented at the Alzheimer’s Association International Conference, recruited 30 pairs of patients and their caregivers. The approach is based on the Dunn model of sensory processing, which focuses on altering environments to maximize chances of success. It “explains that sensory processing is the information coming in, and then our ability to regulate and habituate to those sensations (creates) behavior,” Elizabeth Rhodus, MD, PhD, said during her talk. Dr. Rhodus is assistant professor of medicine at the University of Kentucky, Lexington.

Sensory-based interventions are not uncommon, but most are applied to pediatric populations and tend to focus on sensory processing disorders and autism spectrum disorder. The few programs that do focus on adults have varying methods and produce mixed results. Dr. Rhodus thinks that the key to success is individualization of therapy. “You’re going to like a certain sensation, and I might not like it. You can’t put us in the same room and expect the same results. We have to identify the preferences of how people interact with their environment, and what their brain does at a neuroscience level with that information,” she said.
 

Caregiving hacks

The program employs telehealth to work with caregivers so they can also create sensory environments within the home, using environment to trigger behavior.

For example, although individuals with dementia may have reduced response to color, the color red is unique. “Red is a cortical trigger. Red always stands out to people, so in our package that we send out as part of this intervention, we send out a roll of red duct tape,” said Dr. Rhodus.

An example of the use of red was a patient with dementia who had stopped drinking on his own, causing his caregiver daughter to be concerned that he would soon have to enter a nursing home. Examining the room, the occupational therapist realized that the water was kept out of sight, and suggested that the water glass be placed within the patient’s view, atop a square created with the red duct tape.

“These are just some of the simple concepts. They kind of seem easy. Some of my participants call them caregiving hacks, but it’s things that are grounded in neuroscience – how the brain processes the environment, and then how can we plug in supports and cues in whatever area is missing,” said Dr. Rhodus.

In the program, the caregiver fills out several online surveys, and an occupational therapist conducts an interview to identify specific challenges, such as bathing, or using the toilet, or going to church. Then an adult sensory profile reveals how the patient perceives his or her environment. “It’s taking those individual pieces, and then boiling it down to these mechanisms at the behavioral and neuroscience level,” said Dr. Rhodus. She said the entire setup process takes about an hour.
 

Impactful care

The individualized approach of the HARMONY (Helping Older Adults Create and Manage Occupations Successfully) method is promising, according to Monika Gross, executive director of the Poise Project, which uses the Alexander Technique to help people with chronic conditions such as Parkinson’s disease.

“Although it’s always a very simple idea that human beings need sensory processing aspects in their lives, from the time they’re infants through to the end of life, we don’t really focus on the end of life in a way that can bring meaning between the care partner and the person living with dementia. The other thing that was impressive is that this is in a rural community, where there often aren’t a lot of resources available, (such as) classes that the care partner can take their loved one to. So having something where the care partner has some confidence that they can really make an impact in that person that they are seeing decline, that they can see their behavior change [is good],” said Ms. Gross.
 

Empowering caregivers

The study included 30 pairs of patients and caregivers who were randomized to the individualized care (I), standardized care, or a control group. Adherence to weekly visits was high (I, 88%; S, 100%; C, 60%; P = .061). Retention was strong (I, 80%; S, 60%; C, 50%).

“It was feasible ... and at the end, we found a significant improvement in care partner satisfaction. We actually empowered these people to care for their loved ones, and in doing that, and helping them set up environmental cues, it allowed that person to perform at a more independent level,” said Dr. Rhodus.

The trial was only a proof of concept, so although the researchers saw signs of efficacy, it wasn’t powered to show that. They are currently enrolling additional patients and caregivers for larger studies to further test the approach.

Dr. Rhodus and Ms. Gross have no relevant financial disclosures.

An AI-guided analysis of more than 1,000 human lung transcriptomic datasets found that COVID-19 resembles idiopathic pulmonary fibrosis (IPF) at a fundamental level, according to a study published in eBiomedicine, part of The Lancet Discovery Science.

In the aftermath of COVID-19, a significant number of patients develop a fibrotic lung disease, for which insights into pathogenesis, disease models, or treatment options are lacking, according to researchers Dr. Sinha and colleagues. This long-haul form of the disease culminates in a fibrotic type of interstitial lung disease (ILD). While the actual prevalence of post–COVID-19 ILD (PCLD) is still emerging, early analysis indicates that more than a third of COVID-19 survivors develop fibrotic abnormalities, according to the authors.

Previous research has shown that one of the important determinants for PCLD is the duration of disease. Among patients who developed fibrosis, approximately 4% of patients had a disease duration of less than 1 week; approximately 24% had a disease duration between 1 and 3 weeks; and around 61% had a disease duration longer than 3 weeks, the authors stated.

The lung transcriptomic datasets compared in their study were associated with various lung conditions. The researchers used two viral pandemic signatures (ViP and sViP) and one COVID lung-derived signature. They found that the resemblances included that COVID-19 recapitulates the gene expression patterns (ViP and IPF signatures), cytokine storm (IL15-centric), and the AT2 cytopathic changes, for example, injury, DNA damage, arrest in a transient, damage-induced progenitor state, and senescence-associated secretory phenotype (SASP).

In laboratory experiments, Dr. Sinha and colleagues were able to induce these same immunocytopathic features in preclinical COVID-19 models (human adult lung organoid and hamster) and to reverse them in the hamster model with effective anti–CoV-2 therapeutics.

PPI-network analyses pinpointed endoplasmic reticulum (ER) stress as one of the shared early triggers of both IPF and COVID-19, and immunohistochemistry studies validated the same in the lungs of deceased subjects with COVID-19 and the SARS-CoV-2–challenged hamster lungs. Additionally, lungs from transgenic mice, in which ER stress was induced specifically in the AT2 cells, faithfully recapitulated the host immune response and alveolar cytopathic changes that are induced by SARS-CoV-2.

“In this work, we found that a blood-based gene expression biomarker, which works for prognostication in COVID, also works for IPF,” stated corresponding author Pradipta Ghosh, MD, professor in the departments of medicine and cellular and molecular medicine, University of California, San Diego. “If proven in prospective studies, this biomarker could indicate who is at greatest risk for progressive fibrosis and may require lung transplantation,” she said in an interview.

Dr. Ghosh stated further, “When it comes to therapeutics in COVID lung or IPF, we also found that shared fundamental pathogenic mechanisms present excellent opportunities for developing therapeutics that can arrest the fibrogenic drivers in both diseases. One clue that emerged is a specific cytokine that is at the heart of the smoldering inflammation which is invariably associated with fibrosis. That is interleukin 15 [IL-15] and its receptor.” Dr. Ghosh observed that there are two Food and Drug Administration–approved drugs for IPF. “None are very effective in arresting this invariably fatal disease. Hence, finding better options to treat IPF is an urgent and an unmet need.”

Preclinical testing of hypotheses, Dr. Ghosh said, is next on the path to clinical trials. “We have the advantage of using human lung organoids (mini-lungs grown using stem cells) in a dish, adding additional cells to the system (like fibroblasts and immune cells), infecting them with the virus, or subjecting them to the IL-15 cytokine and monitoring lung fibrosis progression in a dish. Anti–IL-15 therapy can then be initiated to observe reversal of the fibrogenic cascade.” Hamsters have also been shown to provide appropriate models for mimicking lung fibrosis, Dr. Ghosh said. 

“The report by Sinha and colleagues describes the fascinating similarities between drivers of post-COVID lung disease and idiopathic pulmonary fibrosis,” stated David Bowton, MD, professor emeritus, section on critical care, department of anesthesiology, Wake Forest University, Winston-Salem, N.C., in an interview. He added that, “Central to the mechanisms of induction of fibrosis in both disorders appears to be endoplasmic reticulum stress in alveolar type II cells (AT2). ER stress induces the unfolded protein response (UPR) that halts protein translation and promotes the degradation of misfolded proteins. Prolonged UPR can reprogram the cell or trigger apoptosis pathways. ER stress in the lung has been reported in a variety of cell lines including AT2 in IPF, bronchial and alveolar epithelial cells in asthma and [chronic obstructive pulmonary disease], and endothelial cells in pulmonary hypertension.”

Dr. Bowton commented further, including a caution, “Sinha and colleagues suggest that the identification of these gene signatures and mechanisms will be a fruitful avenue for developing effective therapeutics for IPF and other fibrotic lung diseases. I am hopeful that these data may offer clues that expedite this process.  However, the redundancy of triggers for effector pathways in biologic systems argues that, even if successful, this will be [a] long and fraught process.”

The research study was supported by National Institutes of Health grants and funding from the Tobacco-Related Disease Research Program.

Dr. Sinha, Dr. Ghosh, and Dr. Bowton reported no relevant disclosures.

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

An AI-guided analysis of more than 1,000 human lung transcriptomic datasets found that COVID-19 resembles idiopathic pulmonary fibrosis (IPF) at a fundamental level, according to a study published in eBiomedicine, part of The Lancet Discovery Science.

In the aftermath of COVID-19, a significant number of patients develop a fibrotic lung disease, for which insights into pathogenesis, disease models, or treatment options are lacking, according to researchers Dr. Sinha and colleagues. This long-haul form of the disease culminates in a fibrotic type of interstitial lung disease (ILD). While the actual prevalence of post–COVID-19 ILD (PCLD) is still emerging, early analysis indicates that more than a third of COVID-19 survivors develop fibrotic abnormalities, according to the authors.

Previous research has shown that one of the important determinants for PCLD is the duration of disease. Among patients who developed fibrosis, approximately 4% of patients had a disease duration of less than 1 week; approximately 24% had a disease duration between 1 and 3 weeks; and around 61% had a disease duration longer than 3 weeks, the authors stated.

The lung transcriptomic datasets compared in their study were associated with various lung conditions. The researchers used two viral pandemic signatures (ViP and sViP) and one COVID lung-derived signature. They found that the resemblances included that COVID-19 recapitulates the gene expression patterns (ViP and IPF signatures), cytokine storm (IL15-centric), and the AT2 cytopathic changes, for example, injury, DNA damage, arrest in a transient, damage-induced progenitor state, and senescence-associated secretory phenotype (SASP).

In laboratory experiments, Dr. Sinha and colleagues were able to induce these same immunocytopathic features in preclinical COVID-19 models (human adult lung organoid and hamster) and to reverse them in the hamster model with effective anti–CoV-2 therapeutics.

PPI-network analyses pinpointed endoplasmic reticulum (ER) stress as one of the shared early triggers of both IPF and COVID-19, and immunohistochemistry studies validated the same in the lungs of deceased subjects with COVID-19 and the SARS-CoV-2–challenged hamster lungs. Additionally, lungs from transgenic mice, in which ER stress was induced specifically in the AT2 cells, faithfully recapitulated the host immune response and alveolar cytopathic changes that are induced by SARS-CoV-2.

“In this work, we found that a blood-based gene expression biomarker, which works for prognostication in COVID, also works for IPF,” stated corresponding author Pradipta Ghosh, MD, professor in the departments of medicine and cellular and molecular medicine, University of California, San Diego. “If proven in prospective studies, this biomarker could indicate who is at greatest risk for progressive fibrosis and may require lung transplantation,” she said in an interview.

Dr. Ghosh stated further, “When it comes to therapeutics in COVID lung or IPF, we also found that shared fundamental pathogenic mechanisms present excellent opportunities for developing therapeutics that can arrest the fibrogenic drivers in both diseases. One clue that emerged is a specific cytokine that is at the heart of the smoldering inflammation which is invariably associated with fibrosis. That is interleukin 15 [IL-15] and its receptor.” Dr. Ghosh observed that there are two Food and Drug Administration–approved drugs for IPF. “None are very effective in arresting this invariably fatal disease. Hence, finding better options to treat IPF is an urgent and an unmet need.”

Preclinical testing of hypotheses, Dr. Ghosh said, is next on the path to clinical trials. “We have the advantage of using human lung organoids (mini-lungs grown using stem cells) in a dish, adding additional cells to the system (like fibroblasts and immune cells), infecting them with the virus, or subjecting them to the IL-15 cytokine and monitoring lung fibrosis progression in a dish. Anti–IL-15 therapy can then be initiated to observe reversal of the fibrogenic cascade.” Hamsters have also been shown to provide appropriate models for mimicking lung fibrosis, Dr. Ghosh said. 

“The report by Sinha and colleagues describes the fascinating similarities between drivers of post-COVID lung disease and idiopathic pulmonary fibrosis,” stated David Bowton, MD, professor emeritus, section on critical care, department of anesthesiology, Wake Forest University, Winston-Salem, N.C., in an interview. He added that, “Central to the mechanisms of induction of fibrosis in both disorders appears to be endoplasmic reticulum stress in alveolar type II cells (AT2). ER stress induces the unfolded protein response (UPR) that halts protein translation and promotes the degradation of misfolded proteins. Prolonged UPR can reprogram the cell or trigger apoptosis pathways. ER stress in the lung has been reported in a variety of cell lines including AT2 in IPF, bronchial and alveolar epithelial cells in asthma and [chronic obstructive pulmonary disease], and endothelial cells in pulmonary hypertension.”

Dr. Bowton commented further, including a caution, “Sinha and colleagues suggest that the identification of these gene signatures and mechanisms will be a fruitful avenue for developing effective therapeutics for IPF and other fibrotic lung diseases. I am hopeful that these data may offer clues that expedite this process.  However, the redundancy of triggers for effector pathways in biologic systems argues that, even if successful, this will be [a] long and fraught process.”

The research study was supported by National Institutes of Health grants and funding from the Tobacco-Related Disease Research Program.

Dr. Sinha, Dr. Ghosh, and Dr. Bowton reported no relevant disclosures.

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

An AI-guided analysis of more than 1,000 human lung transcriptomic datasets found that COVID-19 resembles idiopathic pulmonary fibrosis (IPF) at a fundamental level, according to a study published in eBiomedicine, part of The Lancet Discovery Science.

In the aftermath of COVID-19, a significant number of patients develop a fibrotic lung disease, for which insights into pathogenesis, disease models, or treatment options are lacking, according to researchers Dr. Sinha and colleagues. This long-haul form of the disease culminates in a fibrotic type of interstitial lung disease (ILD). While the actual prevalence of post–COVID-19 ILD (PCLD) is still emerging, early analysis indicates that more than a third of COVID-19 survivors develop fibrotic abnormalities, according to the authors.

Previous research has shown that one of the important determinants for PCLD is the duration of disease. Among patients who developed fibrosis, approximately 4% of patients had a disease duration of less than 1 week; approximately 24% had a disease duration between 1 and 3 weeks; and around 61% had a disease duration longer than 3 weeks, the authors stated.

The lung transcriptomic datasets compared in their study were associated with various lung conditions. The researchers used two viral pandemic signatures (ViP and sViP) and one COVID lung-derived signature. They found that the resemblances included that COVID-19 recapitulates the gene expression patterns (ViP and IPF signatures), cytokine storm (IL15-centric), and the AT2 cytopathic changes, for example, injury, DNA damage, arrest in a transient, damage-induced progenitor state, and senescence-associated secretory phenotype (SASP).

In laboratory experiments, Dr. Sinha and colleagues were able to induce these same immunocytopathic features in preclinical COVID-19 models (human adult lung organoid and hamster) and to reverse them in the hamster model with effective anti–CoV-2 therapeutics.

PPI-network analyses pinpointed endoplasmic reticulum (ER) stress as one of the shared early triggers of both IPF and COVID-19, and immunohistochemistry studies validated the same in the lungs of deceased subjects with COVID-19 and the SARS-CoV-2–challenged hamster lungs. Additionally, lungs from transgenic mice, in which ER stress was induced specifically in the AT2 cells, faithfully recapitulated the host immune response and alveolar cytopathic changes that are induced by SARS-CoV-2.

“In this work, we found that a blood-based gene expression biomarker, which works for prognostication in COVID, also works for IPF,” stated corresponding author Pradipta Ghosh, MD, professor in the departments of medicine and cellular and molecular medicine, University of California, San Diego. “If proven in prospective studies, this biomarker could indicate who is at greatest risk for progressive fibrosis and may require lung transplantation,” she said in an interview.

Dr. Ghosh stated further, “When it comes to therapeutics in COVID lung or IPF, we also found that shared fundamental pathogenic mechanisms present excellent opportunities for developing therapeutics that can arrest the fibrogenic drivers in both diseases. One clue that emerged is a specific cytokine that is at the heart of the smoldering inflammation which is invariably associated with fibrosis. That is interleukin 15 [IL-15] and its receptor.” Dr. Ghosh observed that there are two Food and Drug Administration–approved drugs for IPF. “None are very effective in arresting this invariably fatal disease. Hence, finding better options to treat IPF is an urgent and an unmet need.”

Preclinical testing of hypotheses, Dr. Ghosh said, is next on the path to clinical trials. “We have the advantage of using human lung organoids (mini-lungs grown using stem cells) in a dish, adding additional cells to the system (like fibroblasts and immune cells), infecting them with the virus, or subjecting them to the IL-15 cytokine and monitoring lung fibrosis progression in a dish. Anti–IL-15 therapy can then be initiated to observe reversal of the fibrogenic cascade.” Hamsters have also been shown to provide appropriate models for mimicking lung fibrosis, Dr. Ghosh said. 

“The report by Sinha and colleagues describes the fascinating similarities between drivers of post-COVID lung disease and idiopathic pulmonary fibrosis,” stated David Bowton, MD, professor emeritus, section on critical care, department of anesthesiology, Wake Forest University, Winston-Salem, N.C., in an interview. He added that, “Central to the mechanisms of induction of fibrosis in both disorders appears to be endoplasmic reticulum stress in alveolar type II cells (AT2). ER stress induces the unfolded protein response (UPR) that halts protein translation and promotes the degradation of misfolded proteins. Prolonged UPR can reprogram the cell or trigger apoptosis pathways. ER stress in the lung has been reported in a variety of cell lines including AT2 in IPF, bronchial and alveolar epithelial cells in asthma and [chronic obstructive pulmonary disease], and endothelial cells in pulmonary hypertension.”

Dr. Bowton commented further, including a caution, “Sinha and colleagues suggest that the identification of these gene signatures and mechanisms will be a fruitful avenue for developing effective therapeutics for IPF and other fibrotic lung diseases. I am hopeful that these data may offer clues that expedite this process.  However, the redundancy of triggers for effector pathways in biologic systems argues that, even if successful, this will be [a] long and fraught process.”

The research study was supported by National Institutes of Health grants and funding from the Tobacco-Related Disease Research Program.

Dr. Sinha, Dr. Ghosh, and Dr. Bowton reported no relevant disclosures.

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