Rheumatology News

Are you among the hundreds of millions of people worldwide with low back pain? If so, you may be familiar with standard treatments like surgery, shots, medications, and spinal manipulations. But new research suggests the solution for the world’s leading cause of disability may lie in fixing how the brain and the body communicate.

Setting out to challenge traditional treatments for chronic back pain, scientists across Australia, Europe, and the United States came together to test the effectiveness of altering how neural networks recognize pain for new research published this week in JAMA.

The randomized clinical trial recruited two groups of 138 participants with chronic low back pain, testing one group with a novel method called graded sensorimotor retraining intervention (RESOLVE) and the other with things like mock laser therapy and noninvasive brain stimulation.

The researchers found the RESOLVE 12-week training course resulted in a statistically significant improvement in pain intensity at 18 weeks.

“What we observed in our trial was a clinically meaningful effect on pain intensity and a clinically meaningful effect on disability. People were happier, they reported their backs felt better, and their quality of life was better,” the study’s lead author, James McAuley, PhD, said in a statement. “This is the first new treatment of its kind for back pain.”
 

Brainy talk

Communication between your brain and back changes over time when you have chronic lower back pain, leading the brain to interpret signals from the back differently and change how you move. It is thought that these neural changes make recovery from pain slower and more complicated , according to Neuroscience Research Australia (NeuRA), a nonprofit research institute in Sydney.

“Over time, the back becomes less fit, and the way the back and brain communicate is disrupted in ways that seem to reinforce the notion that the back is vulnerable and needs protecting,” said Dr. McAuley, a professor at the University of New South Wales, Sydney, and a NeuRA senior research scientist. “The treatment we devised aims to break this self-sustaining cycle.”

RESOLVE treatment focuses on improving this transformed brain-back communication by slowly retraining the body and the brain without the use of opioids or surgery. People in the study have reported improved quality of life 1 year later, according to Dr. McAuley.

The researchers said the pain improvement was “modest,” and the method will need to be tested on other patients and conditions. They hope to introduce this new treatment to doctors and physiotherapists within the next 6-9 months and have already enlisted partner organizations to start this process, according to NeuRA.

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

Are you among the hundreds of millions of people worldwide with low back pain? If so, you may be familiar with standard treatments like surgery, shots, medications, and spinal manipulations. But new research suggests the solution for the world’s leading cause of disability may lie in fixing how the brain and the body communicate.

Setting out to challenge traditional treatments for chronic back pain, scientists across Australia, Europe, and the United States came together to test the effectiveness of altering how neural networks recognize pain for new research published this week in JAMA.

The randomized clinical trial recruited two groups of 138 participants with chronic low back pain, testing one group with a novel method called graded sensorimotor retraining intervention (RESOLVE) and the other with things like mock laser therapy and noninvasive brain stimulation.

The researchers found the RESOLVE 12-week training course resulted in a statistically significant improvement in pain intensity at 18 weeks.

“What we observed in our trial was a clinically meaningful effect on pain intensity and a clinically meaningful effect on disability. People were happier, they reported their backs felt better, and their quality of life was better,” the study’s lead author, James McAuley, PhD, said in a statement. “This is the first new treatment of its kind for back pain.”
 

Brainy talk

Communication between your brain and back changes over time when you have chronic lower back pain, leading the brain to interpret signals from the back differently and change how you move. It is thought that these neural changes make recovery from pain slower and more complicated , according to Neuroscience Research Australia (NeuRA), a nonprofit research institute in Sydney.

“Over time, the back becomes less fit, and the way the back and brain communicate is disrupted in ways that seem to reinforce the notion that the back is vulnerable and needs protecting,” said Dr. McAuley, a professor at the University of New South Wales, Sydney, and a NeuRA senior research scientist. “The treatment we devised aims to break this self-sustaining cycle.”

RESOLVE treatment focuses on improving this transformed brain-back communication by slowly retraining the body and the brain without the use of opioids or surgery. People in the study have reported improved quality of life 1 year later, according to Dr. McAuley.

The researchers said the pain improvement was “modest,” and the method will need to be tested on other patients and conditions. They hope to introduce this new treatment to doctors and physiotherapists within the next 6-9 months and have already enlisted partner organizations to start this process, according to NeuRA.

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

Are you among the hundreds of millions of people worldwide with low back pain? If so, you may be familiar with standard treatments like surgery, shots, medications, and spinal manipulations. But new research suggests the solution for the world’s leading cause of disability may lie in fixing how the brain and the body communicate.

Setting out to challenge traditional treatments for chronic back pain, scientists across Australia, Europe, and the United States came together to test the effectiveness of altering how neural networks recognize pain for new research published this week in JAMA.

The randomized clinical trial recruited two groups of 138 participants with chronic low back pain, testing one group with a novel method called graded sensorimotor retraining intervention (RESOLVE) and the other with things like mock laser therapy and noninvasive brain stimulation.

The researchers found the RESOLVE 12-week training course resulted in a statistically significant improvement in pain intensity at 18 weeks.

“What we observed in our trial was a clinically meaningful effect on pain intensity and a clinically meaningful effect on disability. People were happier, they reported their backs felt better, and their quality of life was better,” the study’s lead author, James McAuley, PhD, said in a statement. “This is the first new treatment of its kind for back pain.”
 

Brainy talk

Communication between your brain and back changes over time when you have chronic lower back pain, leading the brain to interpret signals from the back differently and change how you move. It is thought that these neural changes make recovery from pain slower and more complicated , according to Neuroscience Research Australia (NeuRA), a nonprofit research institute in Sydney.

“Over time, the back becomes less fit, and the way the back and brain communicate is disrupted in ways that seem to reinforce the notion that the back is vulnerable and needs protecting,” said Dr. McAuley, a professor at the University of New South Wales, Sydney, and a NeuRA senior research scientist. “The treatment we devised aims to break this self-sustaining cycle.”

RESOLVE treatment focuses on improving this transformed brain-back communication by slowly retraining the body and the brain without the use of opioids or surgery. People in the study have reported improved quality of life 1 year later, according to Dr. McAuley.

The researchers said the pain improvement was “modest,” and the method will need to be tested on other patients and conditions. They hope to introduce this new treatment to doctors and physiotherapists within the next 6-9 months and have already enlisted partner organizations to start this process, according to NeuRA.

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

One in eight adults (12.7%) diagnosed with COVID-19 will likely experience long-term symptoms, a large study published in The Lancet indicates.

The researchers determined that percentage by comparing long-term symptoms in people infected by SARS-CoV-2 with similar symptoms in uninfected people over the same time period.

Among the group of infected study participants in the Netherlands, 21.4% had at least one new or severely increased symptom 3-5 months after infection compared with before infection. When that group of 21.4% was compared with 8.7% of uninfected people in the same study, the researchers were able to calculate a prevalence 12.7% with long COVID.

“This finding shows that post–COVID-19 condition is an urgent problem with a mounting human toll,” the study authors wrote.

The research design was novel, two editorialists said in an accompanying commentary.

Christopher Brightling, PhD, and Rachael Evans, MBChB, PhD, of the Institute for Lung Health, University of Leicester (England), noted: “This is a major advance on prior long COVID prevalence estimates as it includes a matched uninfected group and accounts for symptoms before COVID-19 infection.”
 

Symptoms that persist

The Lancet study found that 3-5 months after COVID (compared with before COVID) and compared with the non-COVID comparison group, the symptoms that persist were chest pain, breathing difficulties, pain when breathing, muscle pain, loss of taste and/or smell, tingling extremities, lump in throat, feeling hot and cold alternately, heavy limbs, and tiredness.

The authors noted that symptoms such as brain fog were found to be relevant to long COVID after the data collection period for this paper and were not included in this research.

Researcher Aranka V. Ballering, MSc, PhD candidate, said in an interview that the researchers found fever is a symptom that is clearly present during the acute phase of the disease and it peaks the day of the COVID-19 diagnosis, but also wears off.

Loss of taste and smell, however, rapidly increases in severity when COVID-19 is diagnosed, but also persists and is still present 3-5 months after COVID.

Ms. Ballering, with the department of psychiatry at the University of Groningen (the Netherlands), said she was surprised by the sex difference made evident in their research: “Women showed more severe persistent symptoms than men.”
 

Closer to a clearer definition

The authors said their findings also pinpoint symptoms that bring us closer to a better definition of long COVID, which has many different definitions globally.

“These symptoms have the highest discriminative ability to distinguish between post–COVID-19 condition and non–COVID-19–related symptoms,” they wrote.

Researchers collected data by asking participants in the northern Netherlands, who were part of the population-based Lifelines COVID-19 study, to regularly complete digital questionnaires on 23 symptoms commonly associated with long COVID. The questionnaire was sent out 24 times to the same people between March 2020 and August 2021. At that time, people had the Alpha or earlier variants.

Participants were considered COVID-19 positive if they had either a positive test or a doctor’s diagnosis of COVID-19.

Of 76,422 study participants, the 5.5% (4,231) who had COVID were matched to 8,462 controls. Researchers accounted for sex, age, and time of completing questionnaires.
 

Effect of hospitalization, vaccination unclear

Ms. Ballering said it’s unclear from this data whether vaccination or whether a person was hospitalized would change the prevalence of persistent symptoms.

Because of the period when the data were collected, “the vast majority of our study population was not fully vaccinated,” she said.

However, she pointed to recent research that shows that immunization against COVID is only partially effective against persistent somatic symptoms after COVID.

Also, only 5% of men and 2.5% of women in the study were hospitalized as a result of COVID-19, so the findings can’t easily be generalized to hospitalized patients.

The Lifelines study was an add-on study to the multidisciplinary, prospective, population-based, observational Dutch Lifelines cohort study examining 167,729 people in the Netherlands. Almost all were White, a limitation of the study, and 58% were female. Average age was 54.

The editorialists also noted additional limitations of the study were that this research “did not fully consider the impact on mental health” and was conducted in one region in the Netherlands.

Janko Nikolich-Žugich, MD, PhD, director of the Aegis Consortium for Pandemic-Free Future and head of the immunobiology department at University of Arizona, Tucson, said in an interview that he agreed with the editorialists that a primary benefit of this study is that it corrected for symptoms people had before COVID, something other studies have not been able to do.

However, he cautioned about generalizing the results for the United States and other countries because of the lack of diversity in the study population with regard to education level, socioeconomic factors, and race. He pointed out that access issues are also different in the Netherlands, which has universal health care.

He said brain fog as a symptom of long COVID is of high interest and will be important to include in future studies that are able to extend the study period.

The work was funded by ZonMw; the Dutch Ministry of Health, Welfare, and Sport; Dutch Ministry of Economic Affairs; University Medical Center Groningen, University of Groningen; and the provinces of Drenthe, Friesland, and Groningen. The study authors and Dr. Nikolich-Žugich have reported no relevant financial relationships. Dr. Brightling has received consultancy and or grants paid to his institution from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Novartis, Chiesi, Genentech, Roche, Sanofi, Regeneron, Mologic, and 4DPharma for asthma and chronic obstructive pulmonary disease research. Dr. Evans has received consultancy fees from AstraZeneca on the topic of long COVID and from GlaxoSmithKline on digital health, and speaker’s fees from Boehringer Ingelheim on long COVID.

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

One in eight adults (12.7%) diagnosed with COVID-19 will likely experience long-term symptoms, a large study published in The Lancet indicates.

The researchers determined that percentage by comparing long-term symptoms in people infected by SARS-CoV-2 with similar symptoms in uninfected people over the same time period.

Among the group of infected study participants in the Netherlands, 21.4% had at least one new or severely increased symptom 3-5 months after infection compared with before infection. When that group of 21.4% was compared with 8.7% of uninfected people in the same study, the researchers were able to calculate a prevalence 12.7% with long COVID.

“This finding shows that post–COVID-19 condition is an urgent problem with a mounting human toll,” the study authors wrote.

The research design was novel, two editorialists said in an accompanying commentary.

Christopher Brightling, PhD, and Rachael Evans, MBChB, PhD, of the Institute for Lung Health, University of Leicester (England), noted: “This is a major advance on prior long COVID prevalence estimates as it includes a matched uninfected group and accounts for symptoms before COVID-19 infection.”
 

Symptoms that persist

The Lancet study found that 3-5 months after COVID (compared with before COVID) and compared with the non-COVID comparison group, the symptoms that persist were chest pain, breathing difficulties, pain when breathing, muscle pain, loss of taste and/or smell, tingling extremities, lump in throat, feeling hot and cold alternately, heavy limbs, and tiredness.

The authors noted that symptoms such as brain fog were found to be relevant to long COVID after the data collection period for this paper and were not included in this research.

Researcher Aranka V. Ballering, MSc, PhD candidate, said in an interview that the researchers found fever is a symptom that is clearly present during the acute phase of the disease and it peaks the day of the COVID-19 diagnosis, but also wears off.

Loss of taste and smell, however, rapidly increases in severity when COVID-19 is diagnosed, but also persists and is still present 3-5 months after COVID.

Ms. Ballering, with the department of psychiatry at the University of Groningen (the Netherlands), said she was surprised by the sex difference made evident in their research: “Women showed more severe persistent symptoms than men.”
 

Closer to a clearer definition

The authors said their findings also pinpoint symptoms that bring us closer to a better definition of long COVID, which has many different definitions globally.

“These symptoms have the highest discriminative ability to distinguish between post–COVID-19 condition and non–COVID-19–related symptoms,” they wrote.

Researchers collected data by asking participants in the northern Netherlands, who were part of the population-based Lifelines COVID-19 study, to regularly complete digital questionnaires on 23 symptoms commonly associated with long COVID. The questionnaire was sent out 24 times to the same people between March 2020 and August 2021. At that time, people had the Alpha or earlier variants.

Participants were considered COVID-19 positive if they had either a positive test or a doctor’s diagnosis of COVID-19.

Of 76,422 study participants, the 5.5% (4,231) who had COVID were matched to 8,462 controls. Researchers accounted for sex, age, and time of completing questionnaires.
 

Effect of hospitalization, vaccination unclear

Ms. Ballering said it’s unclear from this data whether vaccination or whether a person was hospitalized would change the prevalence of persistent symptoms.

Because of the period when the data were collected, “the vast majority of our study population was not fully vaccinated,” she said.

However, she pointed to recent research that shows that immunization against COVID is only partially effective against persistent somatic symptoms after COVID.

Also, only 5% of men and 2.5% of women in the study were hospitalized as a result of COVID-19, so the findings can’t easily be generalized to hospitalized patients.

The Lifelines study was an add-on study to the multidisciplinary, prospective, population-based, observational Dutch Lifelines cohort study examining 167,729 people in the Netherlands. Almost all were White, a limitation of the study, and 58% were female. Average age was 54.

The editorialists also noted additional limitations of the study were that this research “did not fully consider the impact on mental health” and was conducted in one region in the Netherlands.

Janko Nikolich-Žugich, MD, PhD, director of the Aegis Consortium for Pandemic-Free Future and head of the immunobiology department at University of Arizona, Tucson, said in an interview that he agreed with the editorialists that a primary benefit of this study is that it corrected for symptoms people had before COVID, something other studies have not been able to do.

However, he cautioned about generalizing the results for the United States and other countries because of the lack of diversity in the study population with regard to education level, socioeconomic factors, and race. He pointed out that access issues are also different in the Netherlands, which has universal health care.

He said brain fog as a symptom of long COVID is of high interest and will be important to include in future studies that are able to extend the study period.

The work was funded by ZonMw; the Dutch Ministry of Health, Welfare, and Sport; Dutch Ministry of Economic Affairs; University Medical Center Groningen, University of Groningen; and the provinces of Drenthe, Friesland, and Groningen. The study authors and Dr. Nikolich-Žugich have reported no relevant financial relationships. Dr. Brightling has received consultancy and or grants paid to his institution from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Novartis, Chiesi, Genentech, Roche, Sanofi, Regeneron, Mologic, and 4DPharma for asthma and chronic obstructive pulmonary disease research. Dr. Evans has received consultancy fees from AstraZeneca on the topic of long COVID and from GlaxoSmithKline on digital health, and speaker’s fees from Boehringer Ingelheim on long COVID.

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

One in eight adults (12.7%) diagnosed with COVID-19 will likely experience long-term symptoms, a large study published in The Lancet indicates.

The researchers determined that percentage by comparing long-term symptoms in people infected by SARS-CoV-2 with similar symptoms in uninfected people over the same time period.

Among the group of infected study participants in the Netherlands, 21.4% had at least one new or severely increased symptom 3-5 months after infection compared with before infection. When that group of 21.4% was compared with 8.7% of uninfected people in the same study, the researchers were able to calculate a prevalence 12.7% with long COVID.

“This finding shows that post–COVID-19 condition is an urgent problem with a mounting human toll,” the study authors wrote.

The research design was novel, two editorialists said in an accompanying commentary.

Christopher Brightling, PhD, and Rachael Evans, MBChB, PhD, of the Institute for Lung Health, University of Leicester (England), noted: “This is a major advance on prior long COVID prevalence estimates as it includes a matched uninfected group and accounts for symptoms before COVID-19 infection.”
 

Symptoms that persist

The Lancet study found that 3-5 months after COVID (compared with before COVID) and compared with the non-COVID comparison group, the symptoms that persist were chest pain, breathing difficulties, pain when breathing, muscle pain, loss of taste and/or smell, tingling extremities, lump in throat, feeling hot and cold alternately, heavy limbs, and tiredness.

The authors noted that symptoms such as brain fog were found to be relevant to long COVID after the data collection period for this paper and were not included in this research.

Researcher Aranka V. Ballering, MSc, PhD candidate, said in an interview that the researchers found fever is a symptom that is clearly present during the acute phase of the disease and it peaks the day of the COVID-19 diagnosis, but also wears off.

Loss of taste and smell, however, rapidly increases in severity when COVID-19 is diagnosed, but also persists and is still present 3-5 months after COVID.

Ms. Ballering, with the department of psychiatry at the University of Groningen (the Netherlands), said she was surprised by the sex difference made evident in their research: “Women showed more severe persistent symptoms than men.”
 

Closer to a clearer definition

The authors said their findings also pinpoint symptoms that bring us closer to a better definition of long COVID, which has many different definitions globally.

“These symptoms have the highest discriminative ability to distinguish between post–COVID-19 condition and non–COVID-19–related symptoms,” they wrote.

Researchers collected data by asking participants in the northern Netherlands, who were part of the population-based Lifelines COVID-19 study, to regularly complete digital questionnaires on 23 symptoms commonly associated with long COVID. The questionnaire was sent out 24 times to the same people between March 2020 and August 2021. At that time, people had the Alpha or earlier variants.

Participants were considered COVID-19 positive if they had either a positive test or a doctor’s diagnosis of COVID-19.

Of 76,422 study participants, the 5.5% (4,231) who had COVID were matched to 8,462 controls. Researchers accounted for sex, age, and time of completing questionnaires.
 

Effect of hospitalization, vaccination unclear

Ms. Ballering said it’s unclear from this data whether vaccination or whether a person was hospitalized would change the prevalence of persistent symptoms.

Because of the period when the data were collected, “the vast majority of our study population was not fully vaccinated,” she said.

However, she pointed to recent research that shows that immunization against COVID is only partially effective against persistent somatic symptoms after COVID.

Also, only 5% of men and 2.5% of women in the study were hospitalized as a result of COVID-19, so the findings can’t easily be generalized to hospitalized patients.

The Lifelines study was an add-on study to the multidisciplinary, prospective, population-based, observational Dutch Lifelines cohort study examining 167,729 people in the Netherlands. Almost all were White, a limitation of the study, and 58% were female. Average age was 54.

The editorialists also noted additional limitations of the study were that this research “did not fully consider the impact on mental health” and was conducted in one region in the Netherlands.

Janko Nikolich-Žugich, MD, PhD, director of the Aegis Consortium for Pandemic-Free Future and head of the immunobiology department at University of Arizona, Tucson, said in an interview that he agreed with the editorialists that a primary benefit of this study is that it corrected for symptoms people had before COVID, something other studies have not been able to do.

However, he cautioned about generalizing the results for the United States and other countries because of the lack of diversity in the study population with regard to education level, socioeconomic factors, and race. He pointed out that access issues are also different in the Netherlands, which has universal health care.

He said brain fog as a symptom of long COVID is of high interest and will be important to include in future studies that are able to extend the study period.

The work was funded by ZonMw; the Dutch Ministry of Health, Welfare, and Sport; Dutch Ministry of Economic Affairs; University Medical Center Groningen, University of Groningen; and the provinces of Drenthe, Friesland, and Groningen. The study authors and Dr. Nikolich-Žugich have reported no relevant financial relationships. Dr. Brightling has received consultancy and or grants paid to his institution from GlaxoSmithKline, AstraZeneca, Boehringer Ingelheim, Novartis, Chiesi, Genentech, Roche, Sanofi, Regeneron, Mologic, and 4DPharma for asthma and chronic obstructive pulmonary disease research. Dr. Evans has received consultancy fees from AstraZeneca on the topic of long COVID and from GlaxoSmithKline on digital health, and speaker’s fees from Boehringer Ingelheim on long COVID.

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

Treatment with the humanized monoclonal antibody litifilimab improved scores on a validated measure of skin disease activity in an international phase 2 trial of patients with cutaneous lupus erythematosus (CLE).

Improvements in Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity (CLASI-A) scores in patients randomly assigned to receive subcutaneous litifilimab were superior to changes in patients randomly assigned to placebo over the trial period of 16 weeks. The double-blind study was published in the New England Journal of Medicine.

“This validated measure is working, and it’s very important to now go into phase 3 using the instrument that worked in phase 2 to measure improvement in the skin,” Victoria P. Werth, MD, professor of dermatology at the University of Pennsylvania, Philadelphia, and lead author of the study, said in an interview.

Research on lupus erythematosus has focused on systemic lupus erythematosus (SLE), with few randomized controlled trials addressing CLE, she said, and no Food and Drug Administration–approved treatments for CLE in the last 50 years.

Asked to comment on the results, Alisa Femia, MD, associate professor and director of autoimmune connective tissue disease in the department of dermatology at New York University, who was not involved in the research, said it is “exciting to have a trial that specifically investigates the effect of a drug on cutaneous lupus, as well-designed investigations into this potentially disfiguring disease are relatively sparse and novel treatment pathways are needed.”

The investigational drug targets blood dendritic cell antigen 2 (BDCA2) – a receptor expressed solely on the surface of plasmacytoid dendritic cells (pDCs) – and inhibits the production of type 1 interferon and other inflammatory cytokines and chemokines believed to play a major role in the pathogenesis of cutaneous and systemic lupus, the investigators said.

Rheumatologist Edward Vital, MD, who leads a lupus research group at the University of Leeds (England), said he’s most interested in how the therapy works. The “idea [has been] that pDCs are the main source of type 1 interferon. But there’s a lot of data emerging at present that suggests there are many other sources of interferons, and the drug may work in other ways,” Dr. Vital, an associate professor at the university, said in an interview. He was not involved with the study.

“Maybe pDCs have other important roles. Or maybe other cells are targeted by the therapy, too,” he said. “Understanding this will help us understand the pathogenesis of lupus and which patients will benefit the most.”
 

Improvements in CLASI-A scores

Across 54 centers, the study enrolled 132 patients with primarily moderate to severe active subacute CLE or chronic CLE (including discoid lupus erythematosus), or both subacute and chronic CLE with or without systemic manifestations. Active CLE was defined as a score of at least 8 on CLASI-A, which measures erythema and scaling or hypertrophy in 13 skin regions.

Patients were randomly assigned to receive placebo or litifilimab at doses of 50 mg, 150 mg, or 450 mg subcutaneously at weeks 0, 2, 4, 8, and 12. Mean CLASI-A scores at baseline for placebo and each of the dosage groups were 16.5, 15.2, 18.4, and 16.5, respectively.

The investigators used a test of dose-response to assess response across the four groups on the basis of the percent change in CLASI-A scores from baseline to 16 weeks, the primary endpoint. The percent changes in CLASI-A score were –38.8 ± 7.5 in the 50-mg group; –47.9 ± 7.5 in the 150-mg group; –42.5 ± 5.5 in the 450-mg group; and –14.5 ± 6.4 in the placebo group. (Negative value indicates improvement from baseline.)

When compared with placebo, the change in CLASI-A scores in each of the litifilimab groups was –24.3 percentage points for the 50-mg dose (95% confidence interval, –43.7 to –4.9); –33.4 percentage points for the 150-mg dose (95% CI, –52.7 to –14.1); and –28.0 percentage points for the 450-mg dose (95% CI, –44.6 to –11.4).

“All three dosages caused a similar skin response,” said Dr. Werth. “And importantly, the placebo response is fairly low, much lower than in SLE trials, possibly because the background therapies tend to be less overall [including with slightly lower doses of prednisone]. So we can really see the broad effect of the drug.”

Just under half of participants – 42%-48% of patients receiving litifilimab and 42% of those in the placebo group – had concomitant SLE with low to moderate disease activity as measured by the Systemic Lupus Erythematosus Disease Activity Index 2000. Patients could meet SLE criteria based on previous findings, and “didn’t have to have active SLE,” Dr. Werth noted.

The trial allowed background therapy as long as treatment had begun at least 12 weeks before randomization, with a stable dose starting at least 4 weeks before randomization and maintained throughout the trial period.

Most patients had moderate to severe CLE at baseline “despite approximately 90% having received concomitant background therapy and 80% of those participants having received antimalarial drugs, either alone or with other agents,” Dr. Werth and coinvestigators wrote.

CLASI-A has been shown to correlate to patients’ quality of life, Dr. Werth emphasized in the interview.

Most of the reported side effects in the phase 2 CLE trial were mild or moderate. The treatment was associated with three cases of hypersensitivity, three cases of oral herpes infection, and one case of herpes zoster infection. One case of herpes zoster meningitis occurred 4 months after the last dose of litifilimab.

Approximately 10% of study participants who reported race and ethnicity were Black or African American.

Phase 3 trials

The trial was one part of a two-part phase 2 study of litifilimab, named the LILAC trial, sponsored by Biogen. The other part, which will be published separately, involved patients who had SLE with active joint and skin manifestations.

Biogen is currently enrolling patients in phase 3 studies – the TOPAZ-1 and TOPAZ-2 studies – to evaluate the efficacy and safety of the drug in patients with active SLE. As secondary endpoints, both trials will measure the percentage of participants with a CLASI-A score of at least 10 at baseline who achieve improvement in the score, including a 50% improvement from baseline to week 16, Nathalie Franchimont, MD, PhD, of Biogen, a coauthor of the NEJM study, said in an email.

Biogen also has “plans to initiate a pivotal study in CLE this year,” she said.

With respect to the newly published phase 2 study, Dr. Femia said that, while “conclusions about the magnitude of efficacy are difficult to extrapolate in this trial design, there’s reason for cautious optimism.” There is “good theoretical basis to be optimistic about a drug such as litifilimab, that ultimately reduces type 1 interferon response,” she added.

Anifrolumab, a type 1 interferon receptor monoclonal antibody marketed as Saphnelo, was approved by the FDA for SLE in July 2021, but CLE subtypes were not characterized in trials and CLE was not studied independently of SLE, the authors pointed out in their NEJM article.

The study was supported by Biogen. In addition to working with Biogen, Dr. Werth serves as a consultant to Gilead Sciences and other pharmaceutical companies. Dr. Vital has research grants and has received honoraria from AstraZeneca. Dr. Femia disclosed no relevant financial relationships.

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

Treatment with the humanized monoclonal antibody litifilimab improved scores on a validated measure of skin disease activity in an international phase 2 trial of patients with cutaneous lupus erythematosus (CLE).

Improvements in Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity (CLASI-A) scores in patients randomly assigned to receive subcutaneous litifilimab were superior to changes in patients randomly assigned to placebo over the trial period of 16 weeks. The double-blind study was published in the New England Journal of Medicine.

“This validated measure is working, and it’s very important to now go into phase 3 using the instrument that worked in phase 2 to measure improvement in the skin,” Victoria P. Werth, MD, professor of dermatology at the University of Pennsylvania, Philadelphia, and lead author of the study, said in an interview.

Research on lupus erythematosus has focused on systemic lupus erythematosus (SLE), with few randomized controlled trials addressing CLE, she said, and no Food and Drug Administration–approved treatments for CLE in the last 50 years.

Asked to comment on the results, Alisa Femia, MD, associate professor and director of autoimmune connective tissue disease in the department of dermatology at New York University, who was not involved in the research, said it is “exciting to have a trial that specifically investigates the effect of a drug on cutaneous lupus, as well-designed investigations into this potentially disfiguring disease are relatively sparse and novel treatment pathways are needed.”

The investigational drug targets blood dendritic cell antigen 2 (BDCA2) – a receptor expressed solely on the surface of plasmacytoid dendritic cells (pDCs) – and inhibits the production of type 1 interferon and other inflammatory cytokines and chemokines believed to play a major role in the pathogenesis of cutaneous and systemic lupus, the investigators said.

Rheumatologist Edward Vital, MD, who leads a lupus research group at the University of Leeds (England), said he’s most interested in how the therapy works. The “idea [has been] that pDCs are the main source of type 1 interferon. But there’s a lot of data emerging at present that suggests there are many other sources of interferons, and the drug may work in other ways,” Dr. Vital, an associate professor at the university, said in an interview. He was not involved with the study.

“Maybe pDCs have other important roles. Or maybe other cells are targeted by the therapy, too,” he said. “Understanding this will help us understand the pathogenesis of lupus and which patients will benefit the most.”
 

Improvements in CLASI-A scores

Across 54 centers, the study enrolled 132 patients with primarily moderate to severe active subacute CLE or chronic CLE (including discoid lupus erythematosus), or both subacute and chronic CLE with or without systemic manifestations. Active CLE was defined as a score of at least 8 on CLASI-A, which measures erythema and scaling or hypertrophy in 13 skin regions.

Patients were randomly assigned to receive placebo or litifilimab at doses of 50 mg, 150 mg, or 450 mg subcutaneously at weeks 0, 2, 4, 8, and 12. Mean CLASI-A scores at baseline for placebo and each of the dosage groups were 16.5, 15.2, 18.4, and 16.5, respectively.

The investigators used a test of dose-response to assess response across the four groups on the basis of the percent change in CLASI-A scores from baseline to 16 weeks, the primary endpoint. The percent changes in CLASI-A score were –38.8 ± 7.5 in the 50-mg group; –47.9 ± 7.5 in the 150-mg group; –42.5 ± 5.5 in the 450-mg group; and –14.5 ± 6.4 in the placebo group. (Negative value indicates improvement from baseline.)

When compared with placebo, the change in CLASI-A scores in each of the litifilimab groups was –24.3 percentage points for the 50-mg dose (95% confidence interval, –43.7 to –4.9); –33.4 percentage points for the 150-mg dose (95% CI, –52.7 to –14.1); and –28.0 percentage points for the 450-mg dose (95% CI, –44.6 to –11.4).

“All three dosages caused a similar skin response,” said Dr. Werth. “And importantly, the placebo response is fairly low, much lower than in SLE trials, possibly because the background therapies tend to be less overall [including with slightly lower doses of prednisone]. So we can really see the broad effect of the drug.”

Just under half of participants – 42%-48% of patients receiving litifilimab and 42% of those in the placebo group – had concomitant SLE with low to moderate disease activity as measured by the Systemic Lupus Erythematosus Disease Activity Index 2000. Patients could meet SLE criteria based on previous findings, and “didn’t have to have active SLE,” Dr. Werth noted.

The trial allowed background therapy as long as treatment had begun at least 12 weeks before randomization, with a stable dose starting at least 4 weeks before randomization and maintained throughout the trial period.

Most patients had moderate to severe CLE at baseline “despite approximately 90% having received concomitant background therapy and 80% of those participants having received antimalarial drugs, either alone or with other agents,” Dr. Werth and coinvestigators wrote.

CLASI-A has been shown to correlate to patients’ quality of life, Dr. Werth emphasized in the interview.

Most of the reported side effects in the phase 2 CLE trial were mild or moderate. The treatment was associated with three cases of hypersensitivity, three cases of oral herpes infection, and one case of herpes zoster infection. One case of herpes zoster meningitis occurred 4 months after the last dose of litifilimab.

Approximately 10% of study participants who reported race and ethnicity were Black or African American.

Phase 3 trials

The trial was one part of a two-part phase 2 study of litifilimab, named the LILAC trial, sponsored by Biogen. The other part, which will be published separately, involved patients who had SLE with active joint and skin manifestations.

Biogen is currently enrolling patients in phase 3 studies – the TOPAZ-1 and TOPAZ-2 studies – to evaluate the efficacy and safety of the drug in patients with active SLE. As secondary endpoints, both trials will measure the percentage of participants with a CLASI-A score of at least 10 at baseline who achieve improvement in the score, including a 50% improvement from baseline to week 16, Nathalie Franchimont, MD, PhD, of Biogen, a coauthor of the NEJM study, said in an email.

Biogen also has “plans to initiate a pivotal study in CLE this year,” she said.

With respect to the newly published phase 2 study, Dr. Femia said that, while “conclusions about the magnitude of efficacy are difficult to extrapolate in this trial design, there’s reason for cautious optimism.” There is “good theoretical basis to be optimistic about a drug such as litifilimab, that ultimately reduces type 1 interferon response,” she added.

Anifrolumab, a type 1 interferon receptor monoclonal antibody marketed as Saphnelo, was approved by the FDA for SLE in July 2021, but CLE subtypes were not characterized in trials and CLE was not studied independently of SLE, the authors pointed out in their NEJM article.

The study was supported by Biogen. In addition to working with Biogen, Dr. Werth serves as a consultant to Gilead Sciences and other pharmaceutical companies. Dr. Vital has research grants and has received honoraria from AstraZeneca. Dr. Femia disclosed no relevant financial relationships.

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

Treatment with the humanized monoclonal antibody litifilimab improved scores on a validated measure of skin disease activity in an international phase 2 trial of patients with cutaneous lupus erythematosus (CLE).

Improvements in Cutaneous Lupus Erythematosus Disease Area and Severity Index–Activity (CLASI-A) scores in patients randomly assigned to receive subcutaneous litifilimab were superior to changes in patients randomly assigned to placebo over the trial period of 16 weeks. The double-blind study was published in the New England Journal of Medicine.

“This validated measure is working, and it’s very important to now go into phase 3 using the instrument that worked in phase 2 to measure improvement in the skin,” Victoria P. Werth, MD, professor of dermatology at the University of Pennsylvania, Philadelphia, and lead author of the study, said in an interview.

Research on lupus erythematosus has focused on systemic lupus erythematosus (SLE), with few randomized controlled trials addressing CLE, she said, and no Food and Drug Administration–approved treatments for CLE in the last 50 years.

Asked to comment on the results, Alisa Femia, MD, associate professor and director of autoimmune connective tissue disease in the department of dermatology at New York University, who was not involved in the research, said it is “exciting to have a trial that specifically investigates the effect of a drug on cutaneous lupus, as well-designed investigations into this potentially disfiguring disease are relatively sparse and novel treatment pathways are needed.”

The investigational drug targets blood dendritic cell antigen 2 (BDCA2) – a receptor expressed solely on the surface of plasmacytoid dendritic cells (pDCs) – and inhibits the production of type 1 interferon and other inflammatory cytokines and chemokines believed to play a major role in the pathogenesis of cutaneous and systemic lupus, the investigators said.

Rheumatologist Edward Vital, MD, who leads a lupus research group at the University of Leeds (England), said he’s most interested in how the therapy works. The “idea [has been] that pDCs are the main source of type 1 interferon. But there’s a lot of data emerging at present that suggests there are many other sources of interferons, and the drug may work in other ways,” Dr. Vital, an associate professor at the university, said in an interview. He was not involved with the study.

“Maybe pDCs have other important roles. Or maybe other cells are targeted by the therapy, too,” he said. “Understanding this will help us understand the pathogenesis of lupus and which patients will benefit the most.”
 

Improvements in CLASI-A scores

Across 54 centers, the study enrolled 132 patients with primarily moderate to severe active subacute CLE or chronic CLE (including discoid lupus erythematosus), or both subacute and chronic CLE with or without systemic manifestations. Active CLE was defined as a score of at least 8 on CLASI-A, which measures erythema and scaling or hypertrophy in 13 skin regions.

Patients were randomly assigned to receive placebo or litifilimab at doses of 50 mg, 150 mg, or 450 mg subcutaneously at weeks 0, 2, 4, 8, and 12. Mean CLASI-A scores at baseline for placebo and each of the dosage groups were 16.5, 15.2, 18.4, and 16.5, respectively.

The investigators used a test of dose-response to assess response across the four groups on the basis of the percent change in CLASI-A scores from baseline to 16 weeks, the primary endpoint. The percent changes in CLASI-A score were –38.8 ± 7.5 in the 50-mg group; –47.9 ± 7.5 in the 150-mg group; –42.5 ± 5.5 in the 450-mg group; and –14.5 ± 6.4 in the placebo group. (Negative value indicates improvement from baseline.)

When compared with placebo, the change in CLASI-A scores in each of the litifilimab groups was –24.3 percentage points for the 50-mg dose (95% confidence interval, –43.7 to –4.9); –33.4 percentage points for the 150-mg dose (95% CI, –52.7 to –14.1); and –28.0 percentage points for the 450-mg dose (95% CI, –44.6 to –11.4).

“All three dosages caused a similar skin response,” said Dr. Werth. “And importantly, the placebo response is fairly low, much lower than in SLE trials, possibly because the background therapies tend to be less overall [including with slightly lower doses of prednisone]. So we can really see the broad effect of the drug.”

Just under half of participants – 42%-48% of patients receiving litifilimab and 42% of those in the placebo group – had concomitant SLE with low to moderate disease activity as measured by the Systemic Lupus Erythematosus Disease Activity Index 2000. Patients could meet SLE criteria based on previous findings, and “didn’t have to have active SLE,” Dr. Werth noted.

The trial allowed background therapy as long as treatment had begun at least 12 weeks before randomization, with a stable dose starting at least 4 weeks before randomization and maintained throughout the trial period.

Most patients had moderate to severe CLE at baseline “despite approximately 90% having received concomitant background therapy and 80% of those participants having received antimalarial drugs, either alone or with other agents,” Dr. Werth and coinvestigators wrote.

CLASI-A has been shown to correlate to patients’ quality of life, Dr. Werth emphasized in the interview.

Most of the reported side effects in the phase 2 CLE trial were mild or moderate. The treatment was associated with three cases of hypersensitivity, three cases of oral herpes infection, and one case of herpes zoster infection. One case of herpes zoster meningitis occurred 4 months after the last dose of litifilimab.

Approximately 10% of study participants who reported race and ethnicity were Black or African American.

Phase 3 trials

The trial was one part of a two-part phase 2 study of litifilimab, named the LILAC trial, sponsored by Biogen. The other part, which will be published separately, involved patients who had SLE with active joint and skin manifestations.

Biogen is currently enrolling patients in phase 3 studies – the TOPAZ-1 and TOPAZ-2 studies – to evaluate the efficacy and safety of the drug in patients with active SLE. As secondary endpoints, both trials will measure the percentage of participants with a CLASI-A score of at least 10 at baseline who achieve improvement in the score, including a 50% improvement from baseline to week 16, Nathalie Franchimont, MD, PhD, of Biogen, a coauthor of the NEJM study, said in an email.

Biogen also has “plans to initiate a pivotal study in CLE this year,” she said.

With respect to the newly published phase 2 study, Dr. Femia said that, while “conclusions about the magnitude of efficacy are difficult to extrapolate in this trial design, there’s reason for cautious optimism.” There is “good theoretical basis to be optimistic about a drug such as litifilimab, that ultimately reduces type 1 interferon response,” she added.

Anifrolumab, a type 1 interferon receptor monoclonal antibody marketed as Saphnelo, was approved by the FDA for SLE in July 2021, but CLE subtypes were not characterized in trials and CLE was not studied independently of SLE, the authors pointed out in their NEJM article.

The study was supported by Biogen. In addition to working with Biogen, Dr. Werth serves as a consultant to Gilead Sciences and other pharmaceutical companies. Dr. Vital has research grants and has received honoraria from AstraZeneca. Dr. Femia disclosed no relevant financial relationships.

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

A rheumatologist was suspended from a professional society and his license to practice medicine was threatened after he raised concerns about data manipulation in a published study for which he recruited patients, according to documents seen by Retraction Watch. 

The study, “Added Value of Anti-CD74 Autoantibodies in Axial SpondyloArthritis in a Population With Low HLA-B27 Prevalence,” was published in Frontiers in Immunology in 2019 and has been cited 13 times, according to Clarivate’s Web of Science. In its acknowledgments, it listed Fouad Fayad, PhD, a rheumatologist at the University of Saint Joseph and Hotel-Dieu de France University Medical Center in Beirut, as one of the researchers who recruited patients for the trial. 

Dr. Fayad alleged that the researchers tested patient samples multiple times and used a mix of old and new values in their analysis. After he reported his concerns to the journal and then the university, which both concluded that they could not confirm or refute his allegations, he has faced apparent retaliation, including the suspension of his membership in the Lebanese Society of Rheumatology. 

In comments to Retraction Watch, the corresponding author for the study noted that the two investigations did not find data manipulation, and said the issue was “based on a background of personal and professional conflicts.” 

In an April video recorded with Nassim Nicholas Taleb, PhD, a former quant trader and retired distinguished professor of finance and risk engineering at New York University’s Tandon School of Engineering, Dr. Fayad explained that he was originally an author on the paper, but after expressing concerns about the methodology to the other authors, they didn’t respond to him and his name was dropped from the author list without warning or explanation. 

Dr. Taleb also detailed the issues with the study, showing graphs that indicate “very poor correlation” between the old and new test results from participant samples. 

In October 2019, Dr. Fayad contacted Frontiers in Immunology with his concerns. But the journal’s investigation was inconclusive, and a staffer on the research integrity team told him in July 2020 to contact his institution to investigate, according to emails seen by Retraction Watch. 

Dr. Fayad did so, but the University of Saint Joseph “rushed an incomplete investigation,” he said. It began in September of 2021 and concluded 2 months later that the investigation committee could not confirm or disprove Dr. Fayad’s allegations of data manipulation, according to a copy of the report seen by Retraction Watch. He said that their statistical reviewer did not receive all of the relevant documents, although he had provided them to the university. 

A university official sent the findings from the investigation to the Lebanese Order of Physicians – Beirut, which decided to suspend Dr. Fayad’s membership in the Lebanese Society of Rheumatology. It’s “needless to explain the damage resulting from this suspension,” Dr. Fayad said. 

The Beirut organization wrote to the Lebanese Order of Physicians – Tripoli, the body with which Dr. Fayad’s license is registered, informing them of the decision. In a copy of the letter seen by Retraction Watch, the Beirut organization cited the university investigation finding Dr. Fayad’s allegations to be invalid, as well as a letter in which he alleged mismanagement of the rheumatology society, as reasons for the decision, and referred the matter to the Tripoli organization for further investigation. 

Dr. Fayad told us that the letter asking the Tripoli organization to investigate him could have led to the suspension of his license to practice medicine: 

“My license is registered with the Lebanese Order of Physicians – Tripoli. So legally speaking, it is only Tripoli organization that can suspend my license/permit to practice. Beirut Organization has tried to summon me to their investigation committee, but my license (being registered in Tripoli Organization) does not fall under Beirut’s jurisdiction; in other words Beirut Organization violated the law; they can not approach me directly, they have to go through the Tripoli Organization.

“As such, and since Beirut organization could not suspend my license (as they did for my membership in the Lebanese Society of Rheumatology) they sent the letter to Tripoli organization asking them to investigate the matter and take necessary disciplinary action. This was a threat to suspending my license to practice medicine. Should Tripoli Organization have used the [University of Saint Joseph] letter and investigation report without conducting their own international investigation, my permit to practice would have been suspended.”

The Lebanese Order of Physicians – Tripoli conducted its own investigation and confirmed “the existence of manipulation in the study data and failure to respect the data integrity,” according to an official translation of the investigation report seen by Retraction Watch. The Lebanese Order of Physicians – Tripoli decided after its investigation that Dr. Fayad’s suspension from the rheumatology society was invalid. 

The lead author of the study in question, Nelly R. Ziade of Saint Joseph University and Hotel-Dieu de France Hospital in Beirut, told Retraction Watch that the investigation by the Lebanese Order of Physicians – Tripoli “cannot be considered as final or official” and that she was “never approached, interviewed, or asked to provide any documents related to this complaint.”

She continued: “I will always be available to give any scientific clarification requested by the Order of Physicians in Beirut where a serious investigation giving equal voice to both parties is currently conducted.

“Kindly note that the concerned journal has already conducted an internal investigation where both parties provided all documents and it was concluded that there was no scientific foundation for the accusations.

“Again, a similar investigation was conducted by the Saint-Joseph University in Beirut (where myself and the other party work). Both parties presented study documents to a committee including the president of the IRB, the vice president of the University, the medical director of the University Hospital, experts in musculoskeletal system and biostatistics. In brief, the case against the authors was dismissed, no data manipulation was found and the colleague from Tripoli also was submitted to University sanctions. The report of the University can be shared with you should you need it.

“I’m afraid that this issue is based on a background of personal and professional conflicts.”

Dr. Fayad added: “The beauty of science is that the truth will always prevail and cannot be obscured for long time.”

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

A rheumatologist was suspended from a professional society and his license to practice medicine was threatened after he raised concerns about data manipulation in a published study for which he recruited patients, according to documents seen by Retraction Watch. 

The study, “Added Value of Anti-CD74 Autoantibodies in Axial SpondyloArthritis in a Population With Low HLA-B27 Prevalence,” was published in Frontiers in Immunology in 2019 and has been cited 13 times, according to Clarivate’s Web of Science. In its acknowledgments, it listed Fouad Fayad, PhD, a rheumatologist at the University of Saint Joseph and Hotel-Dieu de France University Medical Center in Beirut, as one of the researchers who recruited patients for the trial. 

Dr. Fayad alleged that the researchers tested patient samples multiple times and used a mix of old and new values in their analysis. After he reported his concerns to the journal and then the university, which both concluded that they could not confirm or refute his allegations, he has faced apparent retaliation, including the suspension of his membership in the Lebanese Society of Rheumatology. 

In comments to Retraction Watch, the corresponding author for the study noted that the two investigations did not find data manipulation, and said the issue was “based on a background of personal and professional conflicts.” 

In an April video recorded with Nassim Nicholas Taleb, PhD, a former quant trader and retired distinguished professor of finance and risk engineering at New York University’s Tandon School of Engineering, Dr. Fayad explained that he was originally an author on the paper, but after expressing concerns about the methodology to the other authors, they didn’t respond to him and his name was dropped from the author list without warning or explanation. 

Dr. Taleb also detailed the issues with the study, showing graphs that indicate “very poor correlation” between the old and new test results from participant samples. 

In October 2019, Dr. Fayad contacted Frontiers in Immunology with his concerns. But the journal’s investigation was inconclusive, and a staffer on the research integrity team told him in July 2020 to contact his institution to investigate, according to emails seen by Retraction Watch. 

Dr. Fayad did so, but the University of Saint Joseph “rushed an incomplete investigation,” he said. It began in September of 2021 and concluded 2 months later that the investigation committee could not confirm or disprove Dr. Fayad’s allegations of data manipulation, according to a copy of the report seen by Retraction Watch. He said that their statistical reviewer did not receive all of the relevant documents, although he had provided them to the university. 

A university official sent the findings from the investigation to the Lebanese Order of Physicians – Beirut, which decided to suspend Dr. Fayad’s membership in the Lebanese Society of Rheumatology. It’s “needless to explain the damage resulting from this suspension,” Dr. Fayad said. 

The Beirut organization wrote to the Lebanese Order of Physicians – Tripoli, the body with which Dr. Fayad’s license is registered, informing them of the decision. In a copy of the letter seen by Retraction Watch, the Beirut organization cited the university investigation finding Dr. Fayad’s allegations to be invalid, as well as a letter in which he alleged mismanagement of the rheumatology society, as reasons for the decision, and referred the matter to the Tripoli organization for further investigation. 

Dr. Fayad told us that the letter asking the Tripoli organization to investigate him could have led to the suspension of his license to practice medicine: 

“My license is registered with the Lebanese Order of Physicians – Tripoli. So legally speaking, it is only Tripoli organization that can suspend my license/permit to practice. Beirut Organization has tried to summon me to their investigation committee, but my license (being registered in Tripoli Organization) does not fall under Beirut’s jurisdiction; in other words Beirut Organization violated the law; they can not approach me directly, they have to go through the Tripoli Organization.

“As such, and since Beirut organization could not suspend my license (as they did for my membership in the Lebanese Society of Rheumatology) they sent the letter to Tripoli organization asking them to investigate the matter and take necessary disciplinary action. This was a threat to suspending my license to practice medicine. Should Tripoli Organization have used the [University of Saint Joseph] letter and investigation report without conducting their own international investigation, my permit to practice would have been suspended.”

The Lebanese Order of Physicians – Tripoli conducted its own investigation and confirmed “the existence of manipulation in the study data and failure to respect the data integrity,” according to an official translation of the investigation report seen by Retraction Watch. The Lebanese Order of Physicians – Tripoli decided after its investigation that Dr. Fayad’s suspension from the rheumatology society was invalid. 

The lead author of the study in question, Nelly R. Ziade of Saint Joseph University and Hotel-Dieu de France Hospital in Beirut, told Retraction Watch that the investigation by the Lebanese Order of Physicians – Tripoli “cannot be considered as final or official” and that she was “never approached, interviewed, or asked to provide any documents related to this complaint.”

She continued: “I will always be available to give any scientific clarification requested by the Order of Physicians in Beirut where a serious investigation giving equal voice to both parties is currently conducted.

“Kindly note that the concerned journal has already conducted an internal investigation where both parties provided all documents and it was concluded that there was no scientific foundation for the accusations.

“Again, a similar investigation was conducted by the Saint-Joseph University in Beirut (where myself and the other party work). Both parties presented study documents to a committee including the president of the IRB, the vice president of the University, the medical director of the University Hospital, experts in musculoskeletal system and biostatistics. In brief, the case against the authors was dismissed, no data manipulation was found and the colleague from Tripoli also was submitted to University sanctions. The report of the University can be shared with you should you need it.

“I’m afraid that this issue is based on a background of personal and professional conflicts.”

Dr. Fayad added: “The beauty of science is that the truth will always prevail and cannot be obscured for long time.”

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

A rheumatologist was suspended from a professional society and his license to practice medicine was threatened after he raised concerns about data manipulation in a published study for which he recruited patients, according to documents seen by Retraction Watch. 

The study, “Added Value of Anti-CD74 Autoantibodies in Axial SpondyloArthritis in a Population With Low HLA-B27 Prevalence,” was published in Frontiers in Immunology in 2019 and has been cited 13 times, according to Clarivate’s Web of Science. In its acknowledgments, it listed Fouad Fayad, PhD, a rheumatologist at the University of Saint Joseph and Hotel-Dieu de France University Medical Center in Beirut, as one of the researchers who recruited patients for the trial. 

Dr. Fayad alleged that the researchers tested patient samples multiple times and used a mix of old and new values in their analysis. After he reported his concerns to the journal and then the university, which both concluded that they could not confirm or refute his allegations, he has faced apparent retaliation, including the suspension of his membership in the Lebanese Society of Rheumatology. 

In comments to Retraction Watch, the corresponding author for the study noted that the two investigations did not find data manipulation, and said the issue was “based on a background of personal and professional conflicts.” 

In an April video recorded with Nassim Nicholas Taleb, PhD, a former quant trader and retired distinguished professor of finance and risk engineering at New York University’s Tandon School of Engineering, Dr. Fayad explained that he was originally an author on the paper, but after expressing concerns about the methodology to the other authors, they didn’t respond to him and his name was dropped from the author list without warning or explanation. 

Dr. Taleb also detailed the issues with the study, showing graphs that indicate “very poor correlation” between the old and new test results from participant samples. 

In October 2019, Dr. Fayad contacted Frontiers in Immunology with his concerns. But the journal’s investigation was inconclusive, and a staffer on the research integrity team told him in July 2020 to contact his institution to investigate, according to emails seen by Retraction Watch. 

Dr. Fayad did so, but the University of Saint Joseph “rushed an incomplete investigation,” he said. It began in September of 2021 and concluded 2 months later that the investigation committee could not confirm or disprove Dr. Fayad’s allegations of data manipulation, according to a copy of the report seen by Retraction Watch. He said that their statistical reviewer did not receive all of the relevant documents, although he had provided them to the university. 

A university official sent the findings from the investigation to the Lebanese Order of Physicians – Beirut, which decided to suspend Dr. Fayad’s membership in the Lebanese Society of Rheumatology. It’s “needless to explain the damage resulting from this suspension,” Dr. Fayad said. 

The Beirut organization wrote to the Lebanese Order of Physicians – Tripoli, the body with which Dr. Fayad’s license is registered, informing them of the decision. In a copy of the letter seen by Retraction Watch, the Beirut organization cited the university investigation finding Dr. Fayad’s allegations to be invalid, as well as a letter in which he alleged mismanagement of the rheumatology society, as reasons for the decision, and referred the matter to the Tripoli organization for further investigation. 

Dr. Fayad told us that the letter asking the Tripoli organization to investigate him could have led to the suspension of his license to practice medicine: 

“My license is registered with the Lebanese Order of Physicians – Tripoli. So legally speaking, it is only Tripoli organization that can suspend my license/permit to practice. Beirut Organization has tried to summon me to their investigation committee, but my license (being registered in Tripoli Organization) does not fall under Beirut’s jurisdiction; in other words Beirut Organization violated the law; they can not approach me directly, they have to go through the Tripoli Organization.

“As such, and since Beirut organization could not suspend my license (as they did for my membership in the Lebanese Society of Rheumatology) they sent the letter to Tripoli organization asking them to investigate the matter and take necessary disciplinary action. This was a threat to suspending my license to practice medicine. Should Tripoli Organization have used the [University of Saint Joseph] letter and investigation report without conducting their own international investigation, my permit to practice would have been suspended.”

The Lebanese Order of Physicians – Tripoli conducted its own investigation and confirmed “the existence of manipulation in the study data and failure to respect the data integrity,” according to an official translation of the investigation report seen by Retraction Watch. The Lebanese Order of Physicians – Tripoli decided after its investigation that Dr. Fayad’s suspension from the rheumatology society was invalid. 

The lead author of the study in question, Nelly R. Ziade of Saint Joseph University and Hotel-Dieu de France Hospital in Beirut, told Retraction Watch that the investigation by the Lebanese Order of Physicians – Tripoli “cannot be considered as final or official” and that she was “never approached, interviewed, or asked to provide any documents related to this complaint.”

She continued: “I will always be available to give any scientific clarification requested by the Order of Physicians in Beirut where a serious investigation giving equal voice to both parties is currently conducted.

“Kindly note that the concerned journal has already conducted an internal investigation where both parties provided all documents and it was concluded that there was no scientific foundation for the accusations.

“Again, a similar investigation was conducted by the Saint-Joseph University in Beirut (where myself and the other party work). Both parties presented study documents to a committee including the president of the IRB, the vice president of the University, the medical director of the University Hospital, experts in musculoskeletal system and biostatistics. In brief, the case against the authors was dismissed, no data manipulation was found and the colleague from Tripoli also was submitted to University sanctions. The report of the University can be shared with you should you need it.

“I’m afraid that this issue is based on a background of personal and professional conflicts.”

Dr. Fayad added: “The beauty of science is that the truth will always prevail and cannot be obscured for long time.”

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

The Pulmonary Fibrosis Foundation (PFF) has launched a new initiative in which they hope to capture a far more diverse representation of patients with pulmonary fibrosis (PF) than the current registry allows them to do, a press release from the PFF indicated.

“The existing registry we have – the PFF Patient Registry – is limited to our care centers, which are primarily academic clinical institutions and we have only a few thousand patients within that registry,” Junelle Speller, MBA, vice president of the PFF Registry, told this news organization.

“We wanted to go beyond these care centers and capture patients in community centers, and in rural settings to provide a more complete understanding of patients with this disease and, of course, have a larger sample size,” she added.

“So, the major impetus behind the PFF Community Registry was to gather a more diverse representative sample of PF patients across all parts of the United States and, most importantly, accelerate the research on PF toward improving earlier diagnosis, treatment, and outcomes for these patients,” Ms. Speller said.
 

Passive versus active

The PFF Community Registry differs in its structure and purpose from the PFF Patient Registry, as Ms. Speller explained. First, the PFF Patient Registry, established in 2016, is “passive” in its nature in that whatever information is entered into a patient’s electronic medical record or clinical chart on a routine office visit is abstracted and captured in the registry. By contrast, the PFF Community Registry is asking for self-reported data from patients, “so it’s more of an ‘active’ registry and will give us a chance to have a bidirectional connection with participants, provide email updates and newsletters, and give patients an opportunity to participate in future studies within the registry as well as in clinical trials,” she noted.

The two registries still overlap in that both capture demographic data on patients’ medical and family histories as well as any medications patients may be taking, but the Community Registry will also capture information with respect to education, employment, patient-reported outcomes, and quality of life metrics. “It will also let us know how patients feel about continued education on the disease itself and patient participation in support groups,” Ms. Speller observed.

The Community Registry will also collect information from lung transplant recipients who have had PF or any other form of interstitial lung disease (ILD) as well as information from caregivers and family members affected by the patient’s disease. As Ms. Speller noted, both PF and other forms of ILD (of which there are more than 200 types) are all characterized by inflammation or scarring in the lung. “Patients are often misdiagnosed, and it can take months, even years, to identify the disease,” Ms. Speller said.

From there, it can be a very long and difficult road ahead, with no cure in sight, although several antifibrotic drugs do help slow disease progression. Typically, onset is around the age of 60 and symptoms include chronic dry cough, fatigue, shortness of breath, weakness, discomfort in the chest, and sometimes unexplained weight loss. Some patients do have a history of smoking, but not all, Ms. Speller noted. So far, registry data suggest PF largely occurs in White patients.

“We’re very excited about the Community Registry, particularly about reaching into communities that we haven’t been able to reach with our existing registry,” Ms. Speller noted. “The rural population in particular is often underserved, so we are really looking forward to capturing data from these patients as well as those from community centers within smaller and larger cities,” she observed.

“A powerful aspect of the Community Registry is that we can use the information gained from it to understand the experience of individuals living with PF, and how it impacts their lives and those of their families and caregivers,” Kevin Flaherty, MD, steering committee chair, PFF Registry, said in a statement.

“Researchers can also look at the data to better understand fibrotic lung diseases and learn about effective approaches to improve patient care,” he added.

Patients who wish to join the PFF Community Registry can sign up at pffregistry.org. To learn more about PF and its risk factors, readers are invited to visit www.AboutPF.org. More than 250,000 patients in the United States are living with either PF or other types of ILD.

Ms. Speller and Dr. Flaherty disclosed no financial conflicts of interest. The PFF Registry is supported by its founding partner, Genentech, Visionary Partner, United Therapeutics, and its sustaining partner, Boehringer Ingelheim, as well as many donors.

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

This article was updated 8/8/22.

The Pulmonary Fibrosis Foundation (PFF) has launched a new initiative in which they hope to capture a far more diverse representation of patients with pulmonary fibrosis (PF) than the current registry allows them to do, a press release from the PFF indicated.

“The existing registry we have – the PFF Patient Registry – is limited to our care centers, which are primarily academic clinical institutions and we have only a few thousand patients within that registry,” Junelle Speller, MBA, vice president of the PFF Registry, told this news organization.

“We wanted to go beyond these care centers and capture patients in community centers, and in rural settings to provide a more complete understanding of patients with this disease and, of course, have a larger sample size,” she added.

“So, the major impetus behind the PFF Community Registry was to gather a more diverse representative sample of PF patients across all parts of the United States and, most importantly, accelerate the research on PF toward improving earlier diagnosis, treatment, and outcomes for these patients,” Ms. Speller said.
 

Passive versus active

The PFF Community Registry differs in its structure and purpose from the PFF Patient Registry, as Ms. Speller explained. First, the PFF Patient Registry, established in 2016, is “passive” in its nature in that whatever information is entered into a patient’s electronic medical record or clinical chart on a routine office visit is abstracted and captured in the registry. By contrast, the PFF Community Registry is asking for self-reported data from patients, “so it’s more of an ‘active’ registry and will give us a chance to have a bidirectional connection with participants, provide email updates and newsletters, and give patients an opportunity to participate in future studies within the registry as well as in clinical trials,” she noted.

The two registries still overlap in that both capture demographic data on patients’ medical and family histories as well as any medications patients may be taking, but the Community Registry will also capture information with respect to education, employment, patient-reported outcomes, and quality of life metrics. “It will also let us know how patients feel about continued education on the disease itself and patient participation in support groups,” Ms. Speller observed.

The Community Registry will also collect information from lung transplant recipients who have had PF or any other form of interstitial lung disease (ILD) as well as information from caregivers and family members affected by the patient’s disease. As Ms. Speller noted, both PF and other forms of ILD (of which there are more than 200 types) are all characterized by inflammation or scarring in the lung. “Patients are often misdiagnosed, and it can take months, even years, to identify the disease,” Ms. Speller said.

From there, it can be a very long and difficult road ahead, with no cure in sight, although several antifibrotic drugs do help slow disease progression. Typically, onset is around the age of 60 and symptoms include chronic dry cough, fatigue, shortness of breath, weakness, discomfort in the chest, and sometimes unexplained weight loss. Some patients do have a history of smoking, but not all, Ms. Speller noted. So far, registry data suggest PF largely occurs in White patients.

“We’re very excited about the Community Registry, particularly about reaching into communities that we haven’t been able to reach with our existing registry,” Ms. Speller noted. “The rural population in particular is often underserved, so we are really looking forward to capturing data from these patients as well as those from community centers within smaller and larger cities,” she observed.

“A powerful aspect of the Community Registry is that we can use the information gained from it to understand the experience of individuals living with PF, and how it impacts their lives and those of their families and caregivers,” Kevin Flaherty, MD, steering committee chair, PFF Registry, said in a statement.

“Researchers can also look at the data to better understand fibrotic lung diseases and learn about effective approaches to improve patient care,” he added.

Patients who wish to join the PFF Community Registry can sign up at pffregistry.org. To learn more about PF and its risk factors, readers are invited to visit www.AboutPF.org. More than 250,000 patients in the United States are living with either PF or other types of ILD.

Ms. Speller and Dr. Flaherty disclosed no financial conflicts of interest. The PFF Registry is supported by its founding partner, Genentech, Visionary Partner, United Therapeutics, and its sustaining partner, Boehringer Ingelheim, as well as many donors.

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

This article was updated 8/8/22.

The Pulmonary Fibrosis Foundation (PFF) has launched a new initiative in which they hope to capture a far more diverse representation of patients with pulmonary fibrosis (PF) than the current registry allows them to do, a press release from the PFF indicated.

“The existing registry we have – the PFF Patient Registry – is limited to our care centers, which are primarily academic clinical institutions and we have only a few thousand patients within that registry,” Junelle Speller, MBA, vice president of the PFF Registry, told this news organization.

“We wanted to go beyond these care centers and capture patients in community centers, and in rural settings to provide a more complete understanding of patients with this disease and, of course, have a larger sample size,” she added.

“So, the major impetus behind the PFF Community Registry was to gather a more diverse representative sample of PF patients across all parts of the United States and, most importantly, accelerate the research on PF toward improving earlier diagnosis, treatment, and outcomes for these patients,” Ms. Speller said.
 

Passive versus active

The PFF Community Registry differs in its structure and purpose from the PFF Patient Registry, as Ms. Speller explained. First, the PFF Patient Registry, established in 2016, is “passive” in its nature in that whatever information is entered into a patient’s electronic medical record or clinical chart on a routine office visit is abstracted and captured in the registry. By contrast, the PFF Community Registry is asking for self-reported data from patients, “so it’s more of an ‘active’ registry and will give us a chance to have a bidirectional connection with participants, provide email updates and newsletters, and give patients an opportunity to participate in future studies within the registry as well as in clinical trials,” she noted.

The two registries still overlap in that both capture demographic data on patients’ medical and family histories as well as any medications patients may be taking, but the Community Registry will also capture information with respect to education, employment, patient-reported outcomes, and quality of life metrics. “It will also let us know how patients feel about continued education on the disease itself and patient participation in support groups,” Ms. Speller observed.

The Community Registry will also collect information from lung transplant recipients who have had PF or any other form of interstitial lung disease (ILD) as well as information from caregivers and family members affected by the patient’s disease. As Ms. Speller noted, both PF and other forms of ILD (of which there are more than 200 types) are all characterized by inflammation or scarring in the lung. “Patients are often misdiagnosed, and it can take months, even years, to identify the disease,” Ms. Speller said.

From there, it can be a very long and difficult road ahead, with no cure in sight, although several antifibrotic drugs do help slow disease progression. Typically, onset is around the age of 60 and symptoms include chronic dry cough, fatigue, shortness of breath, weakness, discomfort in the chest, and sometimes unexplained weight loss. Some patients do have a history of smoking, but not all, Ms. Speller noted. So far, registry data suggest PF largely occurs in White patients.

“We’re very excited about the Community Registry, particularly about reaching into communities that we haven’t been able to reach with our existing registry,” Ms. Speller noted. “The rural population in particular is often underserved, so we are really looking forward to capturing data from these patients as well as those from community centers within smaller and larger cities,” she observed.

“A powerful aspect of the Community Registry is that we can use the information gained from it to understand the experience of individuals living with PF, and how it impacts their lives and those of their families and caregivers,” Kevin Flaherty, MD, steering committee chair, PFF Registry, said in a statement.

“Researchers can also look at the data to better understand fibrotic lung diseases and learn about effective approaches to improve patient care,” he added.

Patients who wish to join the PFF Community Registry can sign up at pffregistry.org. To learn more about PF and its risk factors, readers are invited to visit www.AboutPF.org. More than 250,000 patients in the United States are living with either PF or other types of ILD.

Ms. Speller and Dr. Flaherty disclosed no financial conflicts of interest. The PFF Registry is supported by its founding partner, Genentech, Visionary Partner, United Therapeutics, and its sustaining partner, Boehringer Ingelheim, as well as many donors.

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

This article was updated 8/8/22.

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.

Finding a fiber of good moral fiber

If you’ve ever wandered into the supplement aisle at your local grocery store, you’ve probably noticed an overabundance of fiber supplements that claim to do this for you and benefit that. Since there’s no Food and Drug Administration regulation on fiber supplements, manufacturers are free to (and do) make whatever wild claims they like. And much like choosing which of 500 shows to watch on Netflix, when you’re spoiled for choice, it can be difficult to pick.

Duke University Photo

Enter a team of molecular geneticists and microbiologists from Duke University. They can’t tell you what show to watch next, but they can tell you which fiber to choose, thanks to their new study. And the answer? Yes.

Well that’s not very helpful, but let us explain. For their study, a group of 28 received three of the main fiber supplements (inulin, dextrin, and galactooligosaccharides) for a week each, followed by a week off of fibers for their gut to return to baseline until they’d received all three. Those who consumed the least fiber at baseline saw the greatest benefit from fiber supplementation, with no appreciable difference between the three types. It was the same story for study participants who already consumed enough fiber; because their guts already hosted a more-optimal microbiome, the type of supplement didn’t matter. The benefits were the same across the board.

In an additional study, the Duke researchers found that gut microbiomes reacted to new fiber within a day, being primed to consume fiber on the first dose and digesting it more quickly on the second fiber dose.

The results, the researchers pointed out, make sense, since the average American only consumes 20%-40% of their daily recommended supply of fiber. Our digestive systems aren’t picky; they just want more, so go out there and choose whatever fiber you’d like. Do that, and then feel free to eat as many double bacon cheeseburgers as you’d like. That is the pinnacle of diet right there. Dietitians literally could not complain about it.
 

Jarlsberg vs. Camembert: This time it’s skeletal

Fiber is fabulous, of course, but the road to dietary health and wellness fulfillment takes us to many other, equally wondrous places. Hey, look! This next exit is covered with cheese.

PxHere

All the cheeses are here, from Abbaye de Belloc to Zwitser, and there, right between the jalapeno cheddar and the Jermi tortes you’ll find Jarlsberg, a mild, semisoft, nutty-flavored cheese that comes from Jarlsberg in eastern Norway. A recent study also suggests that Jarlsberg may help to prevent osteopenia and osteoporosis.

A group of Norwegian investigators gathered together 66 healthy women and gave them a daily portion of either Jarlsberg or Camembert for 6 weeks, at which point the Camembert group was switched to Jarlsberg for another 6 weeks.

The research team choose Camembert because of its similarity to Jarlsberg in fat and protein content. Jarlsberg, however, also is rich in vitamin K_{2, which is important for bone health,} and a substance known as DHNA, which “might combat bone thinning and increase bone tissue formation,” they said in a Eurekalert release.

After the first 6 weeks, blood levels of osteocalcin; vitamin K_{2; and} PINP, a peptide involved in bone turnover, were significantly higher in the Jarlsberg group only. All those measures rose significantly after the switch from Camembert to Jarlsberg, while levels of total and LDL cholesterol “fell significantly in the Camembert group after they switched to Jarlsberg,” the team added.

But wait! There’s more! HbA1c fell significantly among those initially eating the Jarlsberg but rose sharply in those eating Camembert. Do you see where this is going? After the Camembert group made the switch to Jarlsberg, their HbA1c levels fell significantly as well.

So it’s not just a cheese thing: The effects are specific to Jarlsberg. Can you guess what we’re having for lunch? Double bacon and fiber Jarlsbergers. Mmm, Jarlsburgers.
 

Luck be a lady: The mother of twins

It’s widely believed that women who have twins must be more fertile, giving birth to more than one child at a time. Some studies have supported the idea, but more recent work is refuting that claim. In actuality, it might just be more statistics and luck than fertility after all.

Michael Blackburn/istockphoto

Those earlier studies supporting fertility didn’t specify whether the chances of twin births were based on the ability to produce more than one egg at a time or on the number of births that women had overall. Looking at 100,000 preindustrial European births, before contraception was available, researchers from Norway, Germany, France, and the United Kingdom found that the number of total births, twins included, makes all the difference.

“When a woman gives birth several times, the chances increase that at least one of these births will be a twin birth,” investigator Gine Roll Skjærvø of the Norwegian University of Science and Technology said in a written statement.

Since twins occur in 1%-3% of all births, the more births that a woman has, the better her chances of giving birth to twins. The researchers compared it to playing the lottery. You buy enough tickets, eventually your numbers are going to come up. Despite that, however, they found that women who give birth to twins give birth less often than those who don’t have twins. Which raises the idea of sheer luck.

The researchers said that there’s still a lot to uncover in twin births, noting that “uncritically comparing groups of women with and without twins can trick us into believing the opposite of what is really true. These groupings may either hide the effects of twinning and fertility genes where they exist, or vice versa, create the illusion of these if they do not exist.”

For now, this new research claims that it’s basically a lottery. And women who give birth to twins hit the jackpot.
 

Those with low wages may be earning future memory loss

Not only are low wages detrimental to our souls, hopes, and dreams, but a new study shows that low wages also are linked to quicker memory decline later in life. Sustained low wages not only cause stress and food insecurity in the lives of many, but they also can cause diseases such as depression, obesity, and high blood pressure, which are risk factors for cognitive aging.

Nicola Barts/Pexels

The study was conducted using records from the Health and Retirement Study for the years 1992-2016 and focused on 2,879 adults born between 1936 and 1941. The participants were divided into three groups: those who never earned low wages, those who sometimes did, and those who always did.

The investigators found that workers who earned sustained low wages – defined as an hourly wage lower than two-thirds of the federal median wage for the corresponding year – “experienced significantly faster memory decline in older age” than did those who never earned low wages.

There are signs of inflation everywhere we look these days, but many people are not earning higher wages to compensate for the extra expenses. “Increasing the federal minimum wage, for example to $15 per hour, remains a gridlock issue in Congress,” lead author Katrina Kezios of the Columbia University Mailman School of Public Health, said in a statement released by the university.

If only salaries would rise instead of prices for once.

Finding a fiber of good moral fiber

If you’ve ever wandered into the supplement aisle at your local grocery store, you’ve probably noticed an overabundance of fiber supplements that claim to do this for you and benefit that. Since there’s no Food and Drug Administration regulation on fiber supplements, manufacturers are free to (and do) make whatever wild claims they like. And much like choosing which of 500 shows to watch on Netflix, when you’re spoiled for choice, it can be difficult to pick.

Duke University Photo

Enter a team of molecular geneticists and microbiologists from Duke University. They can’t tell you what show to watch next, but they can tell you which fiber to choose, thanks to their new study. And the answer? Yes.

Well that’s not very helpful, but let us explain. For their study, a group of 28 received three of the main fiber supplements (inulin, dextrin, and galactooligosaccharides) for a week each, followed by a week off of fibers for their gut to return to baseline until they’d received all three. Those who consumed the least fiber at baseline saw the greatest benefit from fiber supplementation, with no appreciable difference between the three types. It was the same story for study participants who already consumed enough fiber; because their guts already hosted a more-optimal microbiome, the type of supplement didn’t matter. The benefits were the same across the board.

In an additional study, the Duke researchers found that gut microbiomes reacted to new fiber within a day, being primed to consume fiber on the first dose and digesting it more quickly on the second fiber dose.

The results, the researchers pointed out, make sense, since the average American only consumes 20%-40% of their daily recommended supply of fiber. Our digestive systems aren’t picky; they just want more, so go out there and choose whatever fiber you’d like. Do that, and then feel free to eat as many double bacon cheeseburgers as you’d like. That is the pinnacle of diet right there. Dietitians literally could not complain about it.
 

Jarlsberg vs. Camembert: This time it’s skeletal

Fiber is fabulous, of course, but the road to dietary health and wellness fulfillment takes us to many other, equally wondrous places. Hey, look! This next exit is covered with cheese.

PxHere

All the cheeses are here, from Abbaye de Belloc to Zwitser, and there, right between the jalapeno cheddar and the Jermi tortes you’ll find Jarlsberg, a mild, semisoft, nutty-flavored cheese that comes from Jarlsberg in eastern Norway. A recent study also suggests that Jarlsberg may help to prevent osteopenia and osteoporosis.

A group of Norwegian investigators gathered together 66 healthy women and gave them a daily portion of either Jarlsberg or Camembert for 6 weeks, at which point the Camembert group was switched to Jarlsberg for another 6 weeks.

The research team choose Camembert because of its similarity to Jarlsberg in fat and protein content. Jarlsberg, however, also is rich in vitamin K_{2, which is important for bone health,} and a substance known as DHNA, which “might combat bone thinning and increase bone tissue formation,” they said in a Eurekalert release.

After the first 6 weeks, blood levels of osteocalcin; vitamin K_{2; and} PINP, a peptide involved in bone turnover, were significantly higher in the Jarlsberg group only. All those measures rose significantly after the switch from Camembert to Jarlsberg, while levels of total and LDL cholesterol “fell significantly in the Camembert group after they switched to Jarlsberg,” the team added.

But wait! There’s more! HbA1c fell significantly among those initially eating the Jarlsberg but rose sharply in those eating Camembert. Do you see where this is going? After the Camembert group made the switch to Jarlsberg, their HbA1c levels fell significantly as well.

So it’s not just a cheese thing: The effects are specific to Jarlsberg. Can you guess what we’re having for lunch? Double bacon and fiber Jarlsbergers. Mmm, Jarlsburgers.
 

Luck be a lady: The mother of twins

It’s widely believed that women who have twins must be more fertile, giving birth to more than one child at a time. Some studies have supported the idea, but more recent work is refuting that claim. In actuality, it might just be more statistics and luck than fertility after all.

Michael Blackburn/istockphoto

Those earlier studies supporting fertility didn’t specify whether the chances of twin births were based on the ability to produce more than one egg at a time or on the number of births that women had overall. Looking at 100,000 preindustrial European births, before contraception was available, researchers from Norway, Germany, France, and the United Kingdom found that the number of total births, twins included, makes all the difference.

“When a woman gives birth several times, the chances increase that at least one of these births will be a twin birth,” investigator Gine Roll Skjærvø of the Norwegian University of Science and Technology said in a written statement.

Since twins occur in 1%-3% of all births, the more births that a woman has, the better her chances of giving birth to twins. The researchers compared it to playing the lottery. You buy enough tickets, eventually your numbers are going to come up. Despite that, however, they found that women who give birth to twins give birth less often than those who don’t have twins. Which raises the idea of sheer luck.

The researchers said that there’s still a lot to uncover in twin births, noting that “uncritically comparing groups of women with and without twins can trick us into believing the opposite of what is really true. These groupings may either hide the effects of twinning and fertility genes where they exist, or vice versa, create the illusion of these if they do not exist.”

For now, this new research claims that it’s basically a lottery. And women who give birth to twins hit the jackpot.
 

Those with low wages may be earning future memory loss

Not only are low wages detrimental to our souls, hopes, and dreams, but a new study shows that low wages also are linked to quicker memory decline later in life. Sustained low wages not only cause stress and food insecurity in the lives of many, but they also can cause diseases such as depression, obesity, and high blood pressure, which are risk factors for cognitive aging.

Nicola Barts/Pexels

The study was conducted using records from the Health and Retirement Study for the years 1992-2016 and focused on 2,879 adults born between 1936 and 1941. The participants were divided into three groups: those who never earned low wages, those who sometimes did, and those who always did.

The investigators found that workers who earned sustained low wages – defined as an hourly wage lower than two-thirds of the federal median wage for the corresponding year – “experienced significantly faster memory decline in older age” than did those who never earned low wages.

There are signs of inflation everywhere we look these days, but many people are not earning higher wages to compensate for the extra expenses. “Increasing the federal minimum wage, for example to $15 per hour, remains a gridlock issue in Congress,” lead author Katrina Kezios of the Columbia University Mailman School of Public Health, said in a statement released by the university.

If only salaries would rise instead of prices for once.

Finding a fiber of good moral fiber

If you’ve ever wandered into the supplement aisle at your local grocery store, you’ve probably noticed an overabundance of fiber supplements that claim to do this for you and benefit that. Since there’s no Food and Drug Administration regulation on fiber supplements, manufacturers are free to (and do) make whatever wild claims they like. And much like choosing which of 500 shows to watch on Netflix, when you’re spoiled for choice, it can be difficult to pick.

Duke University Photo

Enter a team of molecular geneticists and microbiologists from Duke University. They can’t tell you what show to watch next, but they can tell you which fiber to choose, thanks to their new study. And the answer? Yes.

Well that’s not very helpful, but let us explain. For their study, a group of 28 received three of the main fiber supplements (inulin, dextrin, and galactooligosaccharides) for a week each, followed by a week off of fibers for their gut to return to baseline until they’d received all three. Those who consumed the least fiber at baseline saw the greatest benefit from fiber supplementation, with no appreciable difference between the three types. It was the same story for study participants who already consumed enough fiber; because their guts already hosted a more-optimal microbiome, the type of supplement didn’t matter. The benefits were the same across the board.

In an additional study, the Duke researchers found that gut microbiomes reacted to new fiber within a day, being primed to consume fiber on the first dose and digesting it more quickly on the second fiber dose.

The results, the researchers pointed out, make sense, since the average American only consumes 20%-40% of their daily recommended supply of fiber. Our digestive systems aren’t picky; they just want more, so go out there and choose whatever fiber you’d like. Do that, and then feel free to eat as many double bacon cheeseburgers as you’d like. That is the pinnacle of diet right there. Dietitians literally could not complain about it.
 

Jarlsberg vs. Camembert: This time it’s skeletal

Fiber is fabulous, of course, but the road to dietary health and wellness fulfillment takes us to many other, equally wondrous places. Hey, look! This next exit is covered with cheese.

PxHere

All the cheeses are here, from Abbaye de Belloc to Zwitser, and there, right between the jalapeno cheddar and the Jermi tortes you’ll find Jarlsberg, a mild, semisoft, nutty-flavored cheese that comes from Jarlsberg in eastern Norway. A recent study also suggests that Jarlsberg may help to prevent osteopenia and osteoporosis.

A group of Norwegian investigators gathered together 66 healthy women and gave them a daily portion of either Jarlsberg or Camembert for 6 weeks, at which point the Camembert group was switched to Jarlsberg for another 6 weeks.

The research team choose Camembert because of its similarity to Jarlsberg in fat and protein content. Jarlsberg, however, also is rich in vitamin K_{2, which is important for bone health,} and a substance known as DHNA, which “might combat bone thinning and increase bone tissue formation,” they said in a Eurekalert release.

After the first 6 weeks, blood levels of osteocalcin; vitamin K_{2; and} PINP, a peptide involved in bone turnover, were significantly higher in the Jarlsberg group only. All those measures rose significantly after the switch from Camembert to Jarlsberg, while levels of total and LDL cholesterol “fell significantly in the Camembert group after they switched to Jarlsberg,” the team added.

But wait! There’s more! HbA1c fell significantly among those initially eating the Jarlsberg but rose sharply in those eating Camembert. Do you see where this is going? After the Camembert group made the switch to Jarlsberg, their HbA1c levels fell significantly as well.

So it’s not just a cheese thing: The effects are specific to Jarlsberg. Can you guess what we’re having for lunch? Double bacon and fiber Jarlsbergers. Mmm, Jarlsburgers.
 

Luck be a lady: The mother of twins

It’s widely believed that women who have twins must be more fertile, giving birth to more than one child at a time. Some studies have supported the idea, but more recent work is refuting that claim. In actuality, it might just be more statistics and luck than fertility after all.

Michael Blackburn/istockphoto

Those earlier studies supporting fertility didn’t specify whether the chances of twin births were based on the ability to produce more than one egg at a time or on the number of births that women had overall. Looking at 100,000 preindustrial European births, before contraception was available, researchers from Norway, Germany, France, and the United Kingdom found that the number of total births, twins included, makes all the difference.

“When a woman gives birth several times, the chances increase that at least one of these births will be a twin birth,” investigator Gine Roll Skjærvø of the Norwegian University of Science and Technology said in a written statement.

Since twins occur in 1%-3% of all births, the more births that a woman has, the better her chances of giving birth to twins. The researchers compared it to playing the lottery. You buy enough tickets, eventually your numbers are going to come up. Despite that, however, they found that women who give birth to twins give birth less often than those who don’t have twins. Which raises the idea of sheer luck.

The researchers said that there’s still a lot to uncover in twin births, noting that “uncritically comparing groups of women with and without twins can trick us into believing the opposite of what is really true. These groupings may either hide the effects of twinning and fertility genes where they exist, or vice versa, create the illusion of these if they do not exist.”

For now, this new research claims that it’s basically a lottery. And women who give birth to twins hit the jackpot.
 

Those with low wages may be earning future memory loss

Not only are low wages detrimental to our souls, hopes, and dreams, but a new study shows that low wages also are linked to quicker memory decline later in life. Sustained low wages not only cause stress and food insecurity in the lives of many, but they also can cause diseases such as depression, obesity, and high blood pressure, which are risk factors for cognitive aging.

Nicola Barts/Pexels

The study was conducted using records from the Health and Retirement Study for the years 1992-2016 and focused on 2,879 adults born between 1936 and 1941. The participants were divided into three groups: those who never earned low wages, those who sometimes did, and those who always did.

The investigators found that workers who earned sustained low wages – defined as an hourly wage lower than two-thirds of the federal median wage for the corresponding year – “experienced significantly faster memory decline in older age” than did those who never earned low wages.

There are signs of inflation everywhere we look these days, but many people are not earning higher wages to compensate for the extra expenses. “Increasing the federal minimum wage, for example to $15 per hour, remains a gridlock issue in Congress,” lead author Katrina Kezios of the Columbia University Mailman School of Public Health, said in a statement released by the university.

If only salaries would rise instead of prices for once.

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.

We all have friends or relatives who, somehow, have managed to avoid catching COVID-19, which has infected more than 91.5 million Americans. You may even be one of the lucky ones yourself.

But health experts are saying: Not so fast. A mounting pile of scientific evidence suggests millions of Americans have been infected with the virus without ever even knowing it because they didn’t have symptoms or had mild cases they mistook for a cold or allergies.

The upshot: These silent COVID-19 cases reflect a hidden side of the pandemic that may be helping to drive new surges and viral variants.

Still, infectious disease experts say there is little doubt that some people have indeed managed to avoid COVID-19 infection altogether, and they are trying to understand why.

Several recent studies have suggested certain genetic and immune system traits may better protect this group of people against the coronavirus, making them less likely than others to be infected or seriously sickened. Researchers around the world are now studying these seemingly super-immune people for clues to what makes them so special, with an eye toward better vaccines, treatments, and prevention strategies.

Infectious disease specialists say both types of cases – those unknowingly infected by COVID-19 and people who’ve avoided the virus altogether – matter greatly to public health, more than 2 years into the pandemic.

“It’s definitely true that some people have had COVID and don’t realize it,” says Stephen Kissler, PhD, an infectious disease researcher with the Harvard T.H. Chan School of Public Health, Boston. “It is potentially good news if there’s more immunity in the population than we realize.”

But he says that being able to identify genetic and other factors that may offer some people protection against COVID-19 is an “exciting prospect” that could help find out who’s most at risk and improve efforts to get the pandemic under control.

Some studies have found a person’s genetic profile, past exposure to other COVID-like viruses, allergies, and even drugs they take for other conditions may all provide some defense – even for people who have not been vaccinated, don’t use masks, or don’t practice social distancing.

A person’s medical history and genetics may help decide their risk from new diseases, meaning “we may be able to help identify people who are at especially high risk from infection,” Dr. Kissler says. “That knowledge could help those people better shield themselves from infection and get quicker access to treatment and vaccines, if necessary. … We don’t yet know, but studies are ongoing for these things.”

Amesh Adalja, MD, an infectious disease specialist with the Johns Hopkins Center for Health Security, Baltimore, agrees that emerging research on people who’ve avoided infection offers the chance of new public health strategies to combat COVID-19.

“I’m sure there is some subset of people who are [COVID] negative,” he says. “So what explains that phenomenon, especially if that person was out there getting significant exposures?”