USA: The RECOVER Initiative - Long Covid research

[Jonathan Edwards]

Just wondering, where's this quote from? How did they determine that this cognitive impairment was "a type of Alzheimer’s disease-related dementia" ?

I don't think we have any real evidence for that. There may be a small number of people who had severe Covid and needed intensive care, with specific neurological lesions, but the main 'brain fog' problem being discussed is not in any way comparable to Alzheimer's as far as I know.

 

[ahimsa]

I don't think we have any real evidence for that. There may be a small number of people who had severe Covid and needed intensive care, with specific neurological lesions, but the main 'brain fog' problem being discussed is not in any way comparable to Alzheimer's as far as I know.

I agree, but I'd like to know the source for the quote.

Which person or organization claimed that this cognitive impairment was a type of dementia?

 

[SNT Gatchaman]

I did a double-take on that too. As Jo says, I don't think for a moment this relates to us. I suspect they're commenting there on the accelerated decline observed in pw Alzheimers [*]. The authors may be misunderstanding what was said or confused about the context and associated role of the US National Institute on Aging. If the authors are unaware of our type of variable cognitive dysfunction, they may naively be assuming that impaired cognition == neurodegeneration.

This is the entire passage —

Trial of baricitinib
Michael Peluso (University of California, San Francisco) described the REVERSE-LC (Randomized Double-Blind Placebo-Controlled Trial Evaluating Baricitinib on Persistent Neurologic and Cardiopulmonary Symptoms of Long COVID) trial that is evaluating baricitinib on persistent neurological and cardiopulmonary symptoms of long COVID. The ongoing clinical study at Vanderbilt University Medical Center is supported by the US National Institute on Aging (NIA) and focuses on long COVID-associated cognitive impairment (a type of Alzheimer’s disease-related dementia). The targeted enrollment is 550 adults, with the primary objective of evaluating safety and efficacy of baricitinib versus placebo on objective neuropsychological outcomes in these individuals. The secondary objective is to determine the effects on physical function, autonomic function, functional status and quality of life. TLC is working with its partner Research Triangle Institute International to add 11 additional sites to accelerate enrollment by more than 1 year in the trial. Tracy Nolen (Research Triangle Institute International) noted that site selection of these additional trial sites is currently ongoing, and the sites will be added to the ongoing trial by 2026. With topline results available in 2028, a potential clear indication that baricitinib is effective in treating these long COVID symptoms could lead to a larger, pivotal TLC clinical trial of this agent.

[*] See eg Alzheimer Disease Patients Who Survived COVID-19 Have Rapid Disease Progression and a Higher Risk of Death at 5-year Follow-up: A Retrospective Cohort Study (2025)

 

[bicentennial]

Sadly, there was talk of neuro-psychiatric psychosis associated with Long Covid. "Alzheimers-associated" implies some pathological finding of neuro-degenerative disease.

But cognitive impairment does not mean dementia, except where someone was trained to assume that it is equivalent, which I found odd and ominous in the administrative procedure of an NHS sub-contractor.

But maybe if its "neuro-cognitive" and someone fuzzy wrote it up for Wes Ely's withdrawn immunomodulation trial at Vanderbilt University Medical Center:

ICH GCP
US Clinical Trials Registry
Clinical Trial NCT05858515

REVERSE-Long COVID-19 With Baricitinib Study (REVERSE-LC)

REVERSE-Long COVID: A Multicenter Randomized, Placebo-Controlled Clinical Trial of Immunomodulation (With Baricitinib) for Long COVID Related Cognitive Impairment and ADRD (Alzheimer's Disease and Related Dementias)

REVERSE-LC is a phase 3 trial of baricitinib versus placebo in adults with neurocognitive impairment (a form of Alzheimer's Disease and Related Dementias or ADRD) or cardiopulmonary symptoms due to Long COVID.

Status - Withdrawn

January 29, 2025 updated by: Wes Ely, Vanderbilt University Medical Center

Eligibility:

Meet the following criteria for "Post-COVID Condition" or Long COVID:

* Cognitive impairment as defined by having at least 20% positive (worse or much worse) items on the ECOG assessment

* Neurocognitive symptoms must have been present for at least 60 days prior to screening. Symptoms that wax and wane must have been initially present at least 60 days prior to screening.

Exclusion:

* Severe cognitive, physical, or psychological disability that would prevent participation in the study


Secondary outcomes (over a 9 month time-frame):

Everyday Cognition: Assess percentage changes of cognitive impairment using Everyday Cognition (ECog) scale in the baricitinib arm compared to the placebo arm from baseline to week 12

Global Neuropsychological Function: Assess percentage changes of global neuropsychological function as measured using the CNS Vital Signs Neurocognition Index cognitive battery between baricitinib and placebo study arm from baseline to week 12.

Post-Exertional Malaise: Assess percentage changes of post-exertional malaise using De Paul Symptom Questionnaire - Post-Exertional Malaise (DSQ-PEM) in the baricitinib arm compared to the placebo arm from baseline to week 12

Symptom Burden: Assess percentage changes of post COVID-19 symptom burden using the Symptom Burden Questionnaire for Long COVID (SBQ-LC) Circulation Subscale in the baricitinib arm compared to the placebo arm from baseline to week 12

Inflammation biomarkers: Decreases in plasma biomarkers of inflammation in the baricitinib arm compared to placebo arm from baseline to week 12

Viral Reservoirs: Decreases in viral reservoirs for the baricitinib arm compared to placebo arm from baseline to week 12

Etc:

And see below that the list of Long Covid clinical trials, in several countries, some now recruiting.

Edits: add link, remove boxes

 

[bicentennial]

Sorry, I forgot the link:

REVERSE-Long COVID-19 With Baricitinib Study (REVERSE-LC)

 

[bicentennial]

I think "Status: withdrawn" may mean its closed for further recruitment.

I think we need to know how a diagnosis of Alzheimers and its related dementias is confirmed. I don't trust psychological tests alone to diagnose such things. Too many overlaps and resemblances.

A neuro-cognitive impairment on top of a cognitive impairnent. 2 types of cognition measured by different tests.

No-one says the test subjects must be diagnosed with Alzheimers. But it is said that neuro-cognitive impairment due to Long Covid is a form of Alzheimers and its related dementias.

Neuro-cognitive impairment is being technically equated to Alzheimers and its related dementias - as if this type of impairment must be a neuro-degenerative disease.

So is this is a trial on Alzheimers and its dementias caused by Long Covid, as stated? Or is the neuro-cognitive impairment not necessarily degenerative?

Is Covid like a contact sport that can damage the brain? Prematurely? My government did not tell me that.

The authors may be misunderstanding what was said or confused about the context and associated role of the US National Institute on Aging.

I'm confused too. I read the trial summary several times. The 2 versions of its title refer to LC lung problems, or some selected LC brain problems which both impair cognition and - it is said - degenerate nerves.

The Vanderbilt subjects must all have both brain problems. So another site must be trialling the drug on the lung problems.

REVERSE-Long COVID: A Multicenter Randomized, Placebo-Controlled Clinical Trial of Immunomodulation (With Baricitinib) for Long COVID Related Cognitive Impairment and ADRD (Alzheimer's Disease and Related Dementias)

REVERSE-LC is a phase 3 trial of baricitinib versus placebo in adults with neurocognitive impairment (a form of Alzheimer's Disease and Related Dementias or ADRD) or cardiopulmonary symptoms due to Long COVID.

January 29, 2025 updated by: Wes Ely, Vanderbilt University Medical Center

If the authors are unaware of our type of variable cognitive dysfunction, they may naively be assuming that impaired cognition == neurodegeneration.

The authors and readers of the commentary may not be aware that the selected Long Covid subjects suffer both cognitive and neurocognitive malfunction of the brain.

The selected neuro-cognitive impairment can be variable if it started to "wax and wane" at least 60 days ago. But all subjects must be mentally competent, nevertheless.

I didn't clarify that all the eligibility criteria must be met

Eligibility:

Meet the following criteria for "Post-COVID Condition" or Long COVID:

* Cognitive impairment as defined by having at least 20% positive (worse or much worse) items on the ECOG assessment

* Neurocognitive symptoms must have been present for at least 60 days prior to screening. Symptoms that wax and wane must have been initially present at least 60 days prior to screening.

Exclusion:

* Severe cognitive, physical, or psychological disability that would prevent participation in the study

It is Wes Ely's job to correct any published distortion of Vanderbilt's work, maybe also inform the public what is the difference between cognitive and neuro-cognitive impairments.

And give his public the 18+ age range of so-called LC "dementias". We hear that in the old countries, the other side of the Atlantic, people are doorstepping their doctors complaining of memory problems, and the paediatric Dutch Long Covid is doubled already.

The everyday cognition is measured by an Everyday Cognition (ECog) scale.

The neuro-cognition (equated to a neuro-degenerative disease), is measured by a neuro-psychological test - the CNS Vital Signs Neurocognition Index cognitive battery.

I don't know that neuro-science would agree with neuro-psychology. And neuro-psychiatry. It is neuro-psychology saying: if it looks like dementia then it must be a neuro-degenerative disease.

The autopsies could have resolved this except the trial accepts subjects with previous cognitve impairment - if its got worse since Covid:

Exclusion: Pre-existing cognitive impairment not exacerbated by acute COVID as determined by study physicians after thorough review of participant's history and medical records

What if its similar but not the same. With ME / CFS I've been told its not brain damage. How did who determine that Long Covid is liable to brain damage? Did anyone check? Its a dreadful thing to say if its not true. Or are they just trialling cases of Alzheimers which caught Long Covid.

... ... with the primary objective of evaluating safety and efficacy of baricitinib versus placebo on objective neuropsychological outcomes in these individuals.

The secondary objective is to determine the effects on physical function, autonomic function, functional status and quality of life.

Did Peluso say that, or did the reporter make the mistake or is it my mistake, as it looks like the cognitions are determined as a secondary outcome, whereas the primary outcomes are only safety, compliance, diversity and randomisation (not efficacy). Diversity heh, ssSSSHUSHhh.

 

[Chandelier]

Long COVID’s Shadow Lingers

Long COVID has exposed both the limits of current clinical science and the challenges of pharmaceutical strategy

www.forbes.com

AI summary

• Long COVID remains a major post-pandemic challenge, affecting about 7% of U.S. adults and showing highly varied symptom patterns that complicate diagnosis, treatment, and research.
• NIH RECOVER data identified eight distinct Long COVID trajectories, with many patients experiencing persistent or recurrent symptoms; women and those hospitalized during acute infection face higher risks of severe, long-lasting effects.
• Cognitive rehabilitation trials have yielded disappointing results, as the RECOVER-NEURO Phase 2 study found no measurable improvement from leading cognitive training or stimulation programs despite subjective patient reports of feeling better.
• U.S. health policy is shifting away from mRNA programs, with HHS ending major BARDA mRNA initiatives and prompting companies like Moderna to cut several pipelines, even as the FDA continues to authorize updated mRNA vaccines for new variants.
• Biopharma firms are redirecting investment toward U.S. manufacturing and supply-chain resilience, with major expansions by Novartis and Moderna indicating a strategic pivot toward production capacity amid uncertain R&D returns and the ongoing burden of Long COVID.

 

[Chandelier]

Sadly, there was talk of neuro-psychiatric psychosis associated with Long Covid. "Alzheimers-associated" implies some pathological finding of neuro-degenerative disease.

But cognitive impairment does not mean dementia, except where someone was trained to assume that it is equivalent, which I found odd and ominous in the administrative procedure of an NHS sub-contractor.

But maybe if its "neuro-cognitive" and someone fuzzy wrote it up for Wes Ely's withdrawn immunomodulation trial at Vanderbilt University Medical Center:

ICH GCP
US Clinical Trials Registry
Clinical Trial NCT05858515

REVERSE-Long COVID-19 With Baricitinib Study (REVERSE-LC)

REVERSE-Long COVID: A Multicenter Randomized, Placebo-Controlled Clinical Trial of Immunomodulation (With Baricitinib) for Long COVID Related Cognitive Impairment and ADRD (Alzheimer's Disease and Related Dementias)

REVERSE-LC is a phase 3 trial of baricitinib versus placebo in adults with neurocognitive impairment (a form of Alzheimer's Disease and Related Dementias or ADRD) or cardiopulmonary symptoms due to Long COVID.

Status - Withdrawn

January 29, 2025 updated by: Wes Ely, Vanderbilt University Medical Center

Eligibility:

Meet the following criteria for "Post-COVID Condition" or Long COVID:

* Cognitive impairment as defined by having at least 20% positive (worse or much worse) items on the ECOG assessment

* Neurocognitive symptoms must have been present for at least 60 days prior to screening. Symptoms that wax and wane must have been initially present at least 60 days prior to screening.

Exclusion:

* Severe cognitive, physical, or psychological disability that would prevent participation in the study


Secondary outcomes (over a 9 month time-frame):

Everyday Cognition: Assess percentage changes of cognitive impairment using Everyday Cognition (ECog) scale in the baricitinib arm compared to the placebo arm from baseline to week 12

Global Neuropsychological Function: Assess percentage changes of global neuropsychological function as measured using the CNS Vital Signs Neurocognition Index cognitive battery between baricitinib and placebo study arm from baseline to week 12.

Post-Exertional Malaise: Assess percentage changes of post-exertional malaise using De Paul Symptom Questionnaire - Post-Exertional Malaise (DSQ-PEM) in the baricitinib arm compared to the placebo arm from baseline to week 12

Symptom Burden: Assess percentage changes of post COVID-19 symptom burden using the Symptom Burden Questionnaire for Long COVID (SBQ-LC) Circulation Subscale in the baricitinib arm compared to the placebo arm from baseline to week 12

Inflammation biomarkers: Decreases in plasma biomarkers of inflammation in the baricitinib arm compared to placebo arm from baseline to week 12

Viral Reservoirs: Decreases in viral reservoirs for the baricitinib arm compared to placebo arm from baseline to week 12

Etc:

And see below that the list of Long Covid clinical trials, in several countries, some now recruiting.

Edits: add link, remove boxes

The REVERSE LC study got additional funding.
It also has its own website:

REVERSE-LC

People living with Long COVID are looking for answers. REVERSE-LC is a study to see if a drug called Baricitinib can help.

www.reversinglongcovid.org

From https://news.vumc.org/2026/02/06/va...site-study-of-immunomodulation-in-long-covid/

Vanderbilt Health to lead expanded multisite study of immunomodulation in long COVID​

The public health burden of long COVID is estimated to be the largest seen from an emerging disease in the past century, yet there remain no effective interventions.

In 2024, Vanderbilt Health investigators received funding from the National Institute on Aging (NIA) for a phase 3, multicenter, placebo-controlled trial to evaluate the efficacy of the immunomodulatory drug baricitinib for treating the persistent neurological and cardiopulmonary symptoms of long COVID.

Baricitinib is a Janus kinase (JAK) inhibitor that received FDA-approval to treat acute COVID-19 following a randomized, controlled trial designed and run by an international team including Vanderbilt Health physician-scientist and senior author, E. Wesley Ely, MD, MPH. Ely is the principal investigator for this new LC trial, and patients are being enrolled at Vanderbilt Health and collaborating institutions Emory University, University of Minnesota Twin Cities-Minneapolis and University of California San Francisco.

The Randomized Double-Blind Placebo-Controlled Trial EValuating Baricitinib on PERSistent NEurologic and Cardiopulmonary symptoms of Long COVID (REVERSE-LC) has now received additional funding from the National Institute of Allergy and Infectious Diseases (NIAID) program called RECOVER-Treating Long COVID (RECOVER-TLC) to expand the investigation by working with the NIA to add 13 more enrolling sites throughout the United States.

During a recent organizational meeting at Vanderbilt, Ely told the collaborating scientists, “This is about building a community of like-minded people who are pursuing both great science and humanism. This is the first time in over a century that we have enough patients at the same time with a single IACC (infection-associated chronic condition) to conduct large trials such as REVERSE-LC.

“A leading hypothesis is that long COVID could be caused by viral reservoirs or areas of dormant virus that can evade detection in the body and cause ongoing inflammation, but few large-scale clinical trials to date have tested treatments aimed specifically at immunomodulation,” said Ely.

“Importantly, even when there is no active infection, many of these same health problems may be caused by a similar state of chronic inflammation. The Janus kinase (JAK)-STAT pathway has been shown to drive this inflammatory response and is linked to heart disease, cognitive issues and persistent viral reservoirs.”

REVERSE-LC will include 550 adults 18 and older who have experienced at least one long Covid symptom that is new or has worsened following a confirmed COVID-19 infection. Participants will either receive baricitinib or a placebo. The year-long study will assess the impact of baricitinib on brain function, heart and lung function, and overall quality of life. After baseline, multiple assessments will be taken at three, six and 12 months.

 

[bicentennial]

The REVERSE LC study got additional funding.
It also has its own website:

REVERSE-LC

People living with Long COVID are looking for answers. REVERSE-LC is a study to see if a drug called Baricitinib can help.

www.reversinglongcovid.org

From https://news.vumc.org/2026/02/06/va...site-study-of-immunomodulation-in-long-covid/

"The public health burden of Long Covid is estimated to be the largest seen from an emergent disease in the past century"

People will weep reading that. In full view of the anomaly. Who will tell the anomaly "specialists" who still hog all the ME/CFS clinics and grab for all of the Long Covid subsidy too. Are our local and central governments still hell-bent to shrink provision into a virtual reality.

"yet there remain no effective interventions"

I would run away and hide if it was me demanding into a 6th year that all governments provide LC clinic services as a mental health provision, because, heh, every body has a mind attached.