Live blog: RECOVER-TLC workshop on new Long COVID clinical trials

Researchers and advocates meet near the National Institutes of Health (NIH) campus this week in Bethesda, Maryland for the second RECOVER-Treating Long COVID (TLC) workshop. The two-day event will offer updates on the NIH’s larger $1.8-billion Long COVID research program, called RECOVER, and announce a new set of clinical trials for the disease.

Launched in 2021, RECOVER has drawn criticism for moving slowly and failing to support promising clinical trials for people with Long COVID. Last year, during the first RECOVER-TLC meeting, researchers and advocates met for three days to offer feedback to the NIH and help shape a new set of clinical trials, utilizing $300 million in funding that was allocated to TLC in 2024. Some advocates left “cautiously optimistic” for the next set of interventions.

People with Long COVID submitted hundreds of proposals for interventions they wanted to see trialed last fall and winter. Now, according to an itinerary of the meeting, RECOVER-TLC has decided to invest their funding into interventions including a glucagon-like peptide-1 receptor agonist (GLP-1), stellate ganglion blocks, low-dose naltrexone, and expanded funding for a trial on the JAK inhibitor baricitinib. Prior to the meeting, this agenda has had mixed reactions among people with Long COVID. 

On top of these announcements, the RECOVER-TLC workshop will include updates from the larger RECOVER program and pathobiology research, discussions about biomarkers and clinical trial designs, and conversations that will inform the initiative’s next steps.

The Sick Times’ team is closely following the event: Betsy is attending in person in Bethesda, while the rest of our team watches virtually. Check this article and our social media pages throughout the two-day event to find our takeaways from each session. 

— Miles Griffis

Table of contents (click to jump to each section):
Tuesday, September 9:

• Tuesday, 9:00 – 9:45 a.m. ET: Welcome, Opening Remarks, Patient Perspectives
• 9:45 – 10:30 a.m. ET: Agent prioritization, Long COVID in children
• 10:30 – 11:30 a.m. ET: Discussion on Low-Dose Naltrexone (LDN)
• 11:45 a.m. – 12:30 p.m. ET: Discussion on Baricitinib
• 1:00 – 2:00 p.m. ET: Patient Perspective — Joshua Roman, Cellist, Composer, and Curator
• 2:00 – 2:40 p.m. ET: Discussion on glucagon-like peptide-1 receptor agonists (GLP-1s)
• 2:40 – 3:10 p.m. ET: Discussion on Stellate Ganglion Block
• 3:30 – 4:30 p.m. ET: RECOVER Clinical Trial Updates and Lessons Learned
• 4:30 – 5:00 p.m. ET: RECOVER Observational Cohort Updates

Wednesday, September 10:

• Wednesday, 9:00 – 9:35 a.m. ET: Recap, Patient Perspectives
• 9:35 – 10:30 a.m. ET: Potential Avenues for Future Treatment and Assays
• 10:30 – 11:15 a.m. ET: Discussion of Biomarkers
• 11:15 – 11:45 a.m. ET: Pathobiology Updates
• 12:30 p.m. ET: A note on access
• 12:30 – 1:00 p.m. ET: Discussion on Clinical Trial Design
• 1:00 – 2:25 p.m. ET: Additional Gaps to be Filled by RECOVER-TLC
• 2:25 – 3:00 p.m. ET: RECOVER-TLC Next Steps and How to Proceed

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Tuesday, 9:00 – 9:45 a.m. ET: Welcome, Opening Remarks, Patient Perspectives

The workshop kicked off with opening remarks from NIH director Jay Bhattacharya, Foundation for the National Institutes of Health (FNIH) chief executive officer Julie Gerberding, and National Institute of Allergy and Infectious Diseases (NIAID) acting director Jeffrey Taubenberger. All three speakers, as well as meeting co-chairs Joseph Breen (NIAID) and Upinder Singh (University of Iowa) said that Long COVID is a priority for the NIH, and emphasized the importance of working urgently and partnering with the patient community to design studies.

“Long COVID remains a pressing health priority for the American public,” Bhattacharya said in a pre-recorded address. “We at the NIH are committed not only to understanding this condition, but also to enabling the discovery of treatments that improve lives.” He added that Long COVID “remains a priority for me personally and for the entire NIH” despite changes at the agency. (However, before he became NIH director, Bhattacharya was well-known for COVID-19 and Long COVID denial, through such actions as co-authoring the Great Barrington Declaration.)

In her remarks, Gerberding acknowledged that people with Long COVID want urgent movement on trials. “We wish we could move faster and had more progress to report, but we do have progress,” she said, and noted that she thinks “we’re going to have a very different conversation a year from now” once new trials have started. She asked the workshop audience for candor, creativity, patience, and “most of all, grace … because we are learning as we go.” (FNIH co-directs the RECOVER-TLC initiative with NIAID.)

Meeting co-chairs Breen and Singh introduced the workshop’s goals and structure. The event has three goals, Breen said: 

• Update the Long COVID community on progress made in the last year;
• Solicit community feedback on intervention selections, study design concepts, and other aspects of trials;
• Continue to highlight opportunities for additional trials.

While this event will announce and discuss several upcoming clinical trials, the TLC program has “more space for additional trials,” Breen said, and community feedback will be crucial to developing those studies. The meeting will also feature updates from the larger RECOVER program, including results from cohort studies and pathobiology studies, and discussion of Long COVID in children and pregnant people.

After the introductions, three Long COVID community members shared their experiences, starting with teenager Serena Lin. Lin described “watching from the sidelines” as her friends went on school trips and other activities, switching to an all-online high school, and her hopes to continue studying Japanese and Mandarin. Her father, Justin Lin, also spoke about his experience as a patient caregiver.

Then, Michael Sieverts from the Patient-Led Research Collaborative spoke about the group and the REVERSE-LC trial (studying baricitinib), of which he is a participant. Sieverts said his symptoms were improved “across the board” after starting the trial, noting that he believes he received baricitinib but won’t know for sure until the trial is unblinded after its completion. He complemented the REVERSE-LC team for considering his feedback and his safety, through measures like masking at the study site he has visited.

— Betsy Ladyzhets

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9:45 – 10:30 a.m. ET: Agent prioritization, Long COVID in children

Elizabeth Geerling from the FNIH and John Beigel from NIAID explained how RECOVER-TLC evaluated the many treatment ideas that Long COVID community members had suggested for trials. The presentation concluded with an official announcement of the treatments that TLC has selected for its first clinical trials: low-dose naltrexone (LDN), baricitinib, GLP-1s, and stellate ganglion blocks. 

The agent prioritization process started after last year’s workshop, as people sent submissions in an online form. As of last week, TLC had received 572 treatment submissions from 364 people; the majority of those submitting treatments (72%) were people with Long COVID, followed by smaller proportions from researchers, caregivers, clinicians.

Working groups then reviewed these agents in waves, with groups devoted to different treatment areas such as antivirals and devices. At least three reviewers “independently scored” treatments, and discussed those scores in groups with other reviewers, Geerling said. 

She also shared the makeup of those working groups: 40% of the 105 total members are academic researchers, 26% are people with lived experience, 17% are from industry, and 17% are from the government. Over 21 meetings, groups have gone through 136 submissions so far, she said.

Beigel shared RECOVER-TLC’s principles for agent selection:

• Listen and learn from the community;
• Lead with science — look for interventions supported by underlying biology;
• Target different biological pathways, and use trials to understand how they may contribute to symptoms;
• Work with other investigators when possible.

Working group members had many lively conversations when discussing potential treatments, Beigel said. For example, some reviewers wanted to focus more on novel drugs, while others were more interested in testing drugs already in use by people with Long COVID in formal trials.

And some reviewers advocated for testing combination therapies, while others said they first wanted to see trials show that individual therapies work on their own before trying combinations. Reviewers also discussed drugs’ potential availability after a trial, their costs, drug safety, biomarkers that might be used to determine who is the best fit for a given drug, and endpoints that should be used, Beigel said.

Following the working group prioritization meetings, a scientific oversight committee discussed several interventions in more detail — eventually leading to the four treatments that TLC has selected for its first round of trials. Beigel shared a brief summary of why each treatment rose to the top of RECOVER-TLC’s prioritization process; other presentations later today will go into more detail.

“I fully recognize there’s not going to be agreement [about which treatments to test],” Beigel said. He acknowledged that some Long COVID community members have criticized the trial selections for not being “bold enough,” and added that he’s also received criticism from people who think some interventions (such as baricitinib) are too risky.

Beigel also noted the disappointment from some community members who have wanted to see an antiviral trial from TLC. He explained that the first round of trials does not include an antiviral in part because there are study design and biomarker considerations for researchers to work out first. “We need to understand the populations that have evidence of viral persistence so we can target the right antiviral to the right population,” he said.

In concluding his talk, Beigel noted that the treatment submission form is still open. He encouraged audience members to submit any ideas that they don’t see discussed at the workshop.

Following the process discussion, Rachel Gross, a pediatrician at New York University and leader of RECOVER’s pediatric research, shared an overview of Long COVID in children to set the stage for discussing a LDN trial that will include this group. “Long COVID is a serious pediatric public health crisis,” she said, stating that the prevalence of the disease is now comparable to asthma. She shared results from RECOVER’s research, including prevalence estimates, common symptoms, and how Long COVID impacts children’s daily lives.

Gross emphasized that children with Long COVID need dedicated pediatric trials as well as collaboration between researchers studying the disease in children and adults. She encouraged researchers to include children in clinical trials wherever it’s “scientifically and clinically appropriate.”

— Betsy Ladyzhets

Long COVID is a serious pediatric public health crisis.

Rachel Gross, NYU Langone & RECOVER

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10:30 – 11:30 a.m. ET: Discussion on Low-Dose Naltrexone (LDN)

The workshop’s first trial session focused on low-dose naltrexone (LDN), which RECOVER-TLC will test in a study focusing on children, adolescents, and young adults.

Peter Rowe, a long-time myalgic encephalomyelitis (ME) researcher and pediatrician at Johns Hopkins University, gave the first talk of the session. Rowe is currently optimistic about research into Long COVID and ME, he said, as research has come a long way in understanding the underlying biology of these diseases; when he got into the ME field, funding was limited and many experts dismissed the disease as psychosomatic.

Next, Stephani Stancil, a pediatrician at Children’s Mercy in Kansas City, discussed the scientific basis for testing LDN in children. LDN may help alleviate Long COVID symptoms by stimulating anti-inflammatory activity and modulating the immune system, Stancil said. It has an established safety profile, including in children, though she noted that naltrexone has been studied more in commercially available doses (50 milligrams), while people with Long COVID tend to use it in much lower doses. A new clinical trial focused on children could help further explain how LDN may help improve symptoms and demonstrate its safety and efficacy, she said.

Kay Tomashek from NIAID then shared details about the RECOVER-TLC LDN trial’s design. People with Long COVID ages six to 25 will be eligible to participate, she said, with a focus on those who have fatigue: the trial will use a measurement called the PedsQL Multidimensional Fatigue Scale to screen participants and track changes to their fatigue during the trial. The study will enroll about 1,300 people across around 100 sites; participants will start with a dose of 1.5 milligrams of LDN or placebo and titrate up to 4.5 milligrams over 16 weeks. 

One of the trial’s goals is to develop a “regulatory-grade LDN study product” that may be officially authorized as a Long COVID treatment, Tomashek said. Currently, LDN can be tough for people to access because it’s not commercially available and must be prepared by compounding pharmacies. Developing a specific LDN product may make the drug available more quickly to all people with Long COVID.

Finally, Hiten Naik, a physician from Vancouver Coastal Health, shared updates from the institution’s clinical trial of LDN in adults — one of several trials that are currently ongoing for Long COVID and ME. The study is not complete yet, so he discussed the trial’s design and lessons learned so far. Like RECOVER-TLC’s planned trial, the study lasts 16 weeks and involves participants titrating up from a 1 milligram dose to a 4.5 milligram dose. Some participants will also undergo MRIs, which may lead to information on the neurological effects of LDN, Naik said.

Following the presentations, Megan Carmilani from Long COVID Families discussed unique considerations for testing treatments in children. She explained that family members should be considered in designing pediatric trials, because when one child has Long COVID, it impacts their parents and siblings, too. For example, she said researchers should offer night, weekend, and virtual appointments, so that parents can continue to prioritize their children’s school attendance. Carmilani also noted that describing and monitoring symptoms can be more difficult for children, particularly younger children.

— Heather Hogan & Betsy Ladyzhets

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11:45 a.m. – 12:30 p.m. ET: Discussion on Baricitinib

Following PLRC’s Michael Sievert’s earlier talk sharing his experience in the REVERSE-LC trial, the University of California San Francisco (UCSF)’s Michael Peluso took the stage in person and presented on behalf of the many researchers associated with the baricitinib trial.

Unlike other trials announced today in the workshop, REVERSE-LC is an existing trial, which received funding from the National Institute on Aging in 2023 and is already underway. Peluso explained that the TLC funding will allow the trial to expand with 11 more study sites across the U.S., bringing the total number of sites for the trial to 15. He said the expanded funding and sites will help accelerate the trial, getting results sooner.  

The trial is testing the baricitinib, which is a JAK inhibitor, a type of immunomodulating drug that blocks a specific cell signaling pathway. It is one of three JAK inhibitors being explored in clinical trials; the other two are upanacitinib and abrocitinib. 

JAK inhibitors come with black box warnings, the most severe warning on drugs approved by the Food and Drug Administration (FDA) since they can have severe side effects. Because of this, the trial has a long list of exclusion criteria as well as numerous safety checks for participants of the trial. Peluso said the study will not enroll people who had pre-existing infection-associated chronic conditions that cause cognitive dysfunction, but he hopes future studies can include them, building on lessons from REVERSE-LC.

“We’re also excluding individuals who’ve had a history of recent blood clots, recent malignancy, recent non-COVID infections that were severe, severe cardiovascular disease, and pregnancy,” he said, listing some of the exclusion criteria for the study. 

The trial is assessing the drug under the concept that Long COVID is a type of Alzheimer’s disease and related dementias (ADRDs). “The key principle here is that we believe that Long COVID is a type of ADRD, very much like mild cognitive impairment, HIV, or other infection-associated cognitive impairment, [even] post-ICU syndromes,” Peluso said. “We believe that Long COVID-associated cognitive impairment may be reversible if we target the right mechanisms.”

Peluso explained REVERSE-LC has an extensive set of outcome measures, using tests like tilt table tests, MRIs, lumbar punctures, and more, which will help better understand mechanisms of Long COVID. The study is also receiving support from the Charles M. Valle Foundation for Long COVID Research, who have endowed the Charles M. Valle Biospiratory for Long COVID Science, a biobank of Long COVID samples, for REVERSE-LC. The foundation is named after Valle, who died from complications of Long COVID in 2022. 

During the session’s Q&A, Chloe Decanson asked a question about how the extensive tests and in-person visits will exclude people with severe Long COVID. Peluso said he hoped that the signals from the trial will hopefully help this population of the community, while PLRC co-founder, and one of the trial’s advisor’s, Hannah Davis said, “I think we need trials that are doing both, both intensive testing, like this, and focusing on decentralized homebound patients.”

The session also highlighted how REVERSE-LC worked with patient-researchers on its study design. Davis said that this study was “one of the best times of patient engagement” that she had experienced in five years of work with the patient-led group. The REVERSE-LC team was very open to feedback on topics like testing and utilized PLRC’s engagement scorecards, Davis said. She hopes RECOVER-TLC’s other trials will take similar engagement steps.

— Miles Griffis

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1:00 – 2:00 p.m. ET: Patient Perspective — Joshua Roman, Cellist, Composer, and Curator

Joshua Roman, a cello soloist and composer, shared his Long COVID story and several songs from his new work, “Immunity,” which is adapted from a unique collaboration with Princeton University Concert’s series, Healing With Music. 

Three weeks after a SARS-CoV-2 infection in 2021, Roman found that he couldn’t walk up stairs, couldn’t read, and, due to shaking hands and cognitive impairment, could no longer play the cello. As a professional musician, he’d been practicing at least five hours a day (sometimes up to 14 hours per day) every day, and performing all over the world. He’d never considered that he would have to put his cello away, but after being diagnosed with dysautonomia, and experiencing fatigue unlike anything he’d known prior to COVID-19, his cello case began collecting dust in the corner of his apartment. 

“I’ve never felt so unsure of who I was,” he told the audience. 

Over the past four-and-a-half years, Roman has found his way back to music in what he calls “a journey of vulnerability and healing.” When he began to write “Immunity,” he had the Lord of the Rings score in mind, something “epic with a five-minute cello solo,” but he realized that what he really needed to share with his audience was vulnerability, joy, and hope. 

“This is still hard for me,” he said after his performance today. “In a very real and measurable way, I am not who I was before I got Long COVID. And I will likely never be the same again.”

— Heather Hogan

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2:00 – 2:40 p.m. ET: Discussion on glucagon-like peptide-1 receptor agonists (GLP-1s)

The workshop then moved to another trial session focused on glucagon-like peptide-1 receptor agonists (GLP-1s), which have commonly been prescribed for diabetes and weight loss. 

Clinician David Kaufman from the Center for Complex Diseases presented a short slide deck on his experience prescribing GLP-1s to his patients with Long COVID. As part of a listserv with clinicians treating chronic complex illnesses, he heard several reports of semaglutide, a GLP-1, inducing improvements in fatigue and pain. Ultimately, he primarily began prescribing microdoses of tirzepatide due to fewer side effects and said his patients taking the drug have seen systemic symptom relief.

Kaufman acknowledged that for clinicians whose area of focus is chronic complex illn2:00 – 2:40 p.m. ET: Discussion on glucagon-like peptide-1 receptor agonists (GLP-1s)esses, “so much of our work is trial and error,” particularly as most treatments are prescribed off-label. 

In terms of trial design, Kaufman noted several areas of discussion for NIH to consider while developing the trial: which drug to use (tirzepatide vs. semaglutide), the dose levels and measurements, administration methods, and titration schedules. 

Senior program director at Scripps Research Julia Moore Vogel* also shared some insight into an upcoming Long COVID trial using tirzepatide, which she is directing. The Scripps Research trial, funded by the Schmidt Initiative for Long COVID, will be completely remote and use standard doses. While the trial hasn’t yet started, Vogel encouraged interested community members to sign up for the waitlist.  

Pharmacologist Nigel Greig, who leads the Drug Design & Development Section at the NIH’s National Institute on Aging, also noted that GLP-1s have been approved for usage in adolescents 10 and up for diabetes and 12 and upwards for weight loss. 

A protocol working group has just started meeting to design RECOVER-TLC’s GLP-1 trial, said moderator Agam Rao, with NIAID. The group will “take into consideration all the available data,” she said.

“We’re being led by science here,” she said, adding that there is still a lot unknown about the design of the trial — from which population they’ll focus on to which specific GLP-1 RA will be used. 

*Editor’s note: Julia Moore Vogel is also on The Sick Times’ advisory board.

— James Salanga

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2:40 – 3:10 p.m. ET: Discussion on Stellate Ganglion Block

Opening the discussion on stellate ganglion blocks, Anna Maria Bombardieri of Stanford University School of Medicine gave an overview of the surgical intervention. Stellate ganglion blocks (SGB), she explained, are a minimally invasive, ultrasound-guided intervention in which a provider injects an anesthetic medicine called a “block” into the stellate ganglion, a collection of nerves on the bottom front side of the neck. 

The procedure is commonly used to treat chronic neuropathic pain, as well as other diseases, syndromes, and conditions. 

Bombardieri said that there are several mechanistic hypotheses that may explain how the block improves Long COVID symptoms, including improved perfusion (or blood flow), cytokine modulation, and autonomic balance. Past small studies have shown that the treatment can help with symptoms such as fatigue, cognitive dysfunction, sleep disturbances, and headaches.

In past studies, the block has been proven to be safe when skilled physicians perform the intervention. Still, of the past studies on SGBs so far, only one was a randomized controlled study, Bombardieri said. The new clinical trial would offer more evidence on the treatment, which has helped some people with Long COVID.

A following panel discussion with Luke Liu of Neuroversion and Kyle Kitzmiller, who filled in for his partner Dianna Cowern, shared some of these stories. Cowern, who could not make the meeting, is a well-known science communicator known as “The Physics Girl” who has had severe Long COVID. Kitzmiller shared Cowern’s experience with an SGB, which led to improvements in her symptoms.

Liu began treating people with Long COVID with SGBs in 2021, publishing his first case study on the treatment in December of that year. “After seeing home run after home run in about eight consecutive patients, I decided to go public with my clinical findings,” he said. Since then, he has published more studies on the treatment in Long COVID and ME. In his presentation, he also shared videos of one patient, a 10-year-old child who showed a dramatic improvement after the treatment. 

In a Q&A, Liu said he suspects that the treatment may help with increasing cerebral blood flow in people with Long COVID, leading to symptom improvements.

Other questions and comments during the Q&A, like one question from researcher Nancy Klimas, discussed Horner syndrome, a side effect of SGBs in which an eye and an area around it on one side of the face can droop. Klimas and other attendees suggested that this syndrome could make it difficult to run a placebo arm in a trial, since those who receive the placebo will not get Horner syndrome. 

Other commenters during the discussion talked about how many other people with Long COVID had tried the intervention and did not have significant improvements, like those discussed by the presenters. 

“I see more these blocks in the context of multi-modal treatments,” Bombardieri said, highlighting it will not be a “holy grail” for all people with Long COVID, but could help improve symptoms and quality of life for some.

— Miles Griffs

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3:30 – 4:30 p.m. ET: RECOVER Clinical Trial Updates and Lessons Learned

The workshop then turned to presenting updates from prior RECOVER clinical trials, which the larger program launched in 2023. Eldrin Lewis from the Stanford University School of Medicine presented a top-level summary of how RECOVER’s eight ongoing trials have progressed since last year. Over 100 sites across 40 states and territories participated in at least one of the five protocols (called VITAL, NEURO, AUTONOMIC, SLEEP, and ENERGIZE), with 44% of participants ages 18-45, 45% of participants ages 46-65, and 10% of participants ages 66 and up. 

Enrollment is complete for five out of eight of the ongoing trials, with data collection complete for two of the protocols (VITAL, testing Paxlovid, and NEURO, testing a brain training program). Lewis said NIH expects complete enrollment for the remaining trials by the end of this year, and that all trials will have enough participants to answer primary scientific goals. 

NIH RECOVER expects to have VITAL and NEURO trial results available by late 2025 or early 2026, with the other three protocol results public by spring or summer 2027. 

Following the updates, patient-advocate Mike Zissis spoke about the urgent need for treatments. He expressed disappointment that NIH director Jay Bhattacharya was not at the meeting in person, saying he had questions and demands for the official. Zissis also responded to FNIH CEO Gerberding’s opening remarks from this morning: “We need commitment. We need candor. Patience is growing thin with patients … We’re in years 5 and 6 for the OG [first-wavers].” 

We need commitment. We need candor. Patience is growing thin with patients … We’re in years 5 and 6 for the OG [first-wavers].

Mike Zissis, patient-advocate

Zissis also called for “urgency, focus, and relentlessness,” adding that trial design must be as “un-burdensome as possible to the patients.” He said he’s also hoping trials will expand remote participation wherever possible and be very clear on exclusion and inclusion criteria to avoid unnecessary communication and energy expenditure for both patients and clinics alike.

Dr. Lindsay Baden (from Brigham Women’s Hospital and Harvard Medical School) reflected on RECOVER-VITAL and said he hopes the NIH trials can help distinguish “the bar of improvement that is clinically meaningful,” even as “we don’t know as much as we wish we knew.” 

The Q&A session included a long discussion about ENERGIZE, RECOVER’s trial testing pacing and exercise as Long COVID treatments. After extensive criticism following the trial’s announcement in 2023 from patient-advocates and researchers who warned the trial could harm people with post-exertional malaise, RECOVER extensively redesigned the study, adding a pacing arm (as the study originally was set to only test exercise) and carefully setting inclusion and exclusion criteria to minimize potential harm.

One workshop attendee spoke about her experience being screened for the trial’s exercise arm. She was not immediately excluded despite a ME diagnosis and reporting PEM, she said, but eventually was excluded due to her result on a symptom severity scale. She asked the presenters to clarify the study’s inclusion criteria as well as whether its exercise protocol qualified as graded exercise therapy, which has a history of hurting people with ME. Lewis and session moderator Laurie Gutmann (from Indiana University School of Medicine) responded that people with PEM could participate in ENERGIZE, but that the trial design sought to exclude those who would be harmed by exercise.

When asked to clarify why ENERGIZE continued with a redesign, as opposed to cancelling that trial and redirecting resources elsewhere following the early criticism, Gutmann said that researchers working on the study “really still felt that this was an important treatment.” 

“There were a lot of different concerns about wanting to have a [trialed] medication as opposed to a non-pharmacological intervention,” she said. “After much discussion, we still felt like it was a valid question to answer for this particular symptom of Long COVID. We just needed to design it in a way that would better answer that question.” 

— James Salanga & Betsy Ladyzhets

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4:30 – 5:00 p.m. ET: RECOVER Observational Cohort Updates

Since the meeting was running behind, the session on observational cohort updates was the last on the first day, with pathobiology updates being moved to tomorrow.

Setting the stage on RECOVER cohorts was Torri Metz, of the University of Utah School of Medicine, presenting on the pregnancy cohort of RECOVER. She stated that enrollment of the cohort is complete, with 1,802 participants. Participants’ children  will be followed to four years of age with “in-depth neurodevelopmental assessments comparing those exposed to SARS-CoV-2 with [those] unexposed.”

So far, the program has already answered some research questions. Metz said the prevalence of Long COVID among those who are infected with SARS-CoV-2 during pregnancy was around 9%, with various risk factors. Researchers also found that the prevalence of Long COVID may be different between those who acquired SARS-C0V-2 during pregnancy compared with outside of pregnancy. Lastly, their data suggests that there are no differences in child neurodevelopment between those exposed to SARS-C0V-2 compared to those unexposed at 12 and 18 months of age. 

Metz ended her presentation advocating for the inclusion of  pregnant individuals in clinical trials for Long COVID. “It’ll be critical in terms of access for them to future therapies and our ability to communicate with certainty about the risks and benefits of therapies for pregnant individuals,” she said. 

Next, Jerry Krishnan of the University of Illinois Chicago (UIC) College of Medicine, presented on how the observational data from RECOVER can be used to better inform clinical trials in Long COVID. He said these data can help define outcomes of trials, find out how often those outcomes happen, as well as identify different subgroups and treatments. 

Amy Pope, a co-chair of the Illinois Research Network (ILLInet) PARATROOPers talked about her experience being a part of the RECOVER adult cohort, which she initially wanted to quit. It led to her being asked to run PARATROOPers, a volunteer patient-led group that has helped inform RECOVER through giving input on study objectives and clinical trials. They also work to foster a sense of community by improving communications between RECOVER and trial participants. 

The group has advocated for access to their personal results from the trial and for more improvements to the RECOVER observational study’s questionnaire, including better gender identification categories and more blank space for comments.

 The PARATROOPers also called for public comment periods to make clinical trials more efficient and patient-centric. “You also need us,” she said. “Listen to your patients.”

— Miles Griffis

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Wednesday, 9:00 – 9:35 a.m. ET: Recap, Patient Perspectives

To kick off Wednesday’s sessions, co-chair Joseph Breen gave a recap of the prior day’s highlights. The workshop so far has highlighted Long COVID’s multidimensional impacts on individuals, families, and communities, Breen said, and has demonstrated the need for close partnership between people with lived experience and medical and research professionals as RECOVER-TLC moves forward with its new clinical trials.

“We heard a plea from Dr. Gerberding for grace and patience,” Breen said. “But also Mike Zissis, a patient with lived experience, expressed that it’s frustrating. One thing that’s also being requested in this partnership is urgency.” He also noted that people with Long COVID want the NIH to offer a “long-term commitment” to studying the disease.

Next, two people with Long COVID shared pre-recorded presentations. Despite being labeled as “patient perspectives,” both speakers shared formal presentations reflecting their professional as well as lived experiences. Victoria C., who has severe Long COVID, discussed the need for accessibility in clinical trial design, focusing on post-exertional malaise (PEM). 

Victoria explained how many people with Long COVID cannot leave their beds, much less travel to a research site for a clinical trial; and for others, participating in a trial could lead to prolonged PEM. PEM and other access needs “should not be an afterthought but should be considered when designing trials from the start,” she said.

She recommended that trials allow more time for participants to complete study tests, test people at home, and require acute COVID-19 measures (such as high-quality masks), provide multiple versions of consent documents for people with different communication needs, and compensate participants for at the least exertional transport to study sites. “I’m shocked that this has to be said, but giving someone COVID at a Long COVID trial is really, really atrocious, guys,” she said. Victoria’s presentation is also available online.

Letícia Soares from the Patient-Led Research Collaborative (PLRC) then discussed equity in clinical trials. Long COVID disproportionately impacts people of color and other marginalized groups, yet “Long COVID biomedical research has an equity issue,” she said: many studies do not accurately reflect patient demographics. She discussed barriers to study participation, including awareness of Long COVID and access to diagnosis, where research mainly takes place, and which patients are involved in designing and validating patient-reported outcomes.

Soares also shared potential solutions for these barriers. To make studies more representative of the Long COVID population, for example, researchers could work with patient researchers from marginalized backgrounds on recruitment and trial design, she said. She also recommended that researchers collaborate across national borders on trials, particularly with scientists and patients in low and middle-income countries. And she called for more research into repurposing drugs from other diseases for Long COVID, as such drugs could be more easily available globally. “Treatments must be accessible to all patients around the world,” she said.

“Those two presentations remind us about all the underserved and marginalized individuals that we have to keep in mind in our studies,” co-chair Upinder Singh said following the presentations.

— Betsy Ladyzhets

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9:35 – 10:30 a.m. ET: Potential Avenues for Future Treatment and Assays

Two talks from leading Long COVID researchers shared potential new study directions. First, David Putrino from Mount Sinai’s Cohen Center for Recovery from Complex Chronic Illnesses spoke on behalf of the SPEAR Study Group, a research collaboration seeking to trial monoclonal antibodies, formed by the biotech company Invivyd.

“Antigen persistence in Long COVID is an under-addressed problem and has been an under-addressed problem from the start,” Putrino said. He provided a brief overview of the persistence theory, explaining that many papers since 2020 have found evidence that the SARS-CoV-2 virus, pieces of it, or its genetic material are circulating in at least some people with Long COVID. Monoclonal antibodies can potentially clear these viral reservoirs, he said.

Putrino then presented a proposed study design from the SPEAR group for a mechanistic clinical trial of a monoclonal antibody, Invivyd’s next-generation product VYD2311 (which improves upon their currently-available product, Pemgarda). “In my personal opinion, the best time for the NIH to have invested in large-scale trials in medications such as monoclonals that can target persistent antigens was in 2021,” Putrino said. “The second best time is right now.”

The goals of SPEAR’s proposed trial would be to determine whether a monoclonal antibody could effectively clear persistent SARS-CoV-2 spike protein in people with Long COVID, then to measure changes in spike levels in correlation with changes in symptoms. The trial design offers a potential “blueprint,” not only for other Long COVID trials but also for other trials looking at different viruses, Putrino said.

SPEAR proposes going directly to a randomized control trial with VYD2311. The trial would recruit up to 400 people with Long COVID who have evidence of viral persistence, as shown with an assay called SIMOA. Patients would take the drug for six months, then go through 18 months of follow-up. Every step of the way, researchers would collect data on participants’ viral reservoirs, immune systems, other circulating pathogens, and more, in order to potentially identify biomarkers that correlate with responding to monoclonal antibodies.

“People with Long COVID have waited long enough for a mechanistic trial of this nature,” Putrino said. “I cannot stress enough how urgent it is that we act right now on a trial of this nature.” Later, during the Q&A portion, he added: “We are effectively begging RECOVER-TLC to throw one monoclonal into the mix.”

Nancy Klimas shared a comment during the Q&A about the monoclonal antibody trial she is leading at Nova Southeastern University. While her trial has a different study design from SPEAR’s proposal, she and her colleagues are collecting an “extensive biorepository” from participants with samples taken before, during, and after the trial, which they will open up to other researchers studying viral persistence, she said.

Steven Deeks then presented about VIPER, a new program under development at the University of California San Francisco (UCSF) aiming to evaluate Long COVID biomarkers. Currently, different Long COVID research groups are independently developing biomarker candidates in their own labs, on their own cohorts; VIPER aims to bring these groups together and test several potential biomarkers on the same cohort, to directly compare them.

VIPER builds on prior UCSF Long COVID research as well as lessons learned from HIV/AIDS, Deeks said. In the 1990s, identifying a surrogate marker (or a marker that indicates a change in symptoms) was key to motivating biopharmaceutical companies to get involved with drug development. Now, as HIV/AIDS research aims to find a cure, scientists have collaborated over the last ten years to find a similar marker for HIV viral reservoirs through a program called RAVEN.

Initially, VIPER would focus on viral persistence as many leading biomarker candidates measure this, Deeks said. Based on prior UCSF work, he and his colleagues propose using viral quantity in patients’ guts as the “gold standard” of persistence, which they would “compare to different blood tests.” But the program could eventually expand from viral persistence to other potential biomarker areas, like immune dysregulation, he said.

The project proposes recruiting at least 150 people (some with Long COVID, some who have “recovered” from a SARS-CoV-2 infection); sending samples from that cohort to teams with promising persistence tests; then doing a “head-to-head comparison” between those tests. Deeks and his colleagues have started to pilot the program already with groups in PolyBio’s Long COVID Consortium, he said.

During the Q&A section, Deeks discussed how VIPER could help researchers better understand different phenotypes of Long COVID, which could inform future clinical trials as well as medical care options.

— Betsy Ladyzhets

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10:30 – 11:15 a.m. ET: Discussion of Biomarkers

Up next, a panel of experts further discussed biomarkers for Long COVID. Joseph Menetski from FNIH started the session by reminding the audience what a biomarker is: he described it as “the link between an objective measurement and a specific clinical decision.” Biomarkers are critically important to answer questions at all points of a patient’s journey, he said, from “who is at risk for a disease?” to “is a treatment working?”

FNIH has a biomarkers consortium that has run for 20 years, Menetski said; it has been “successful in developing validated and qualified biomarkers.” RECOVER-TLC may be able to leverage some of that expertise.

David Price, from Cardiff University, shared an example of biomarker research, summarizing work he and colleagues have done to extensively study the immune systems of people with Long COVID, using samples from a U.K.-based cohort. The group has compiled a wide variety of clinical data and biospecimens from 250 people with Long COVID and 200 “recovered” controls; they have analyzed study participants’ cellular immunity, humoral immunity, protein activation in different areas, and more. One major finding: the group found a “molecular signature of breathlessness,” connected to a protein called CD40 located on T-cells.

In the Q&A section, researchers discussed both recent progress and challenges toward identifying biomarkers. Janko Nikolich, an immunologist at the University of Arizona and co-chair of RECOVER’s pathobiology committee, said that some recent findings are very promising (such as different tests finding viral persistence, immune system markers, and evidence of blood clotting). 

“We need to deliberately invest in biomarkers specifically … so that we can actually use them in trials,” he said. Nikolich also noted that “clusters of markers” may be needed due to Long COVID’s complexity.

Investing in biomarkers will also help incentivize pharmaceutical companies to get more involved with funding Long COVID treatments, said Jessica Martinez, a speaker with lived experience. In particular, biomarkers measuring underlying biological issues in Long COVID would enable pharma companies to develop drugs that address those issues, she said. But any type of biomarker “would engage pharma,” she said, in comparison to the current landscape, in which many companies are hesitant to get involved.

Martinez also noted that some pharmaceutical companies are interested in testing combination therapies (or multiple drugs together), based on conversations she has had with colleagues. “Even if it’s not completely clear in terms of the mechanism, that kind of [combination trial] is something that would get them invested in joining the process,” she said.

Summarizing the session, moderator Jerry Krishnan, from the University of Illinois Chicago, said: “There’s a great need [for biomarkers], an enormous amount of work, great candidates… Now we need to coordinate this effort so we can integrate them into the design of the clinical trials.” As the biomarker session had been cut somewhat short due to other sessions running behind schedule, Krishnan said he hoped that attendees could continue this conversation after the workshop

— Betsy Ladyzhets

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11:15 – 11:45 a.m. ET: Pathobiology Updates

Serena Spudich from the Yale University School of Medicine shared key agreements and disagreements in data from a May 2025 workshop on Long COVID pathobiology. Spudich and Yale’s Akiko Iwasaki hosted the meeting, and were joined by many leading Long COVID researchers. Spudich mentioned that a recording of the workshop was available upon request.

The workshop focused on a variety of topics including the immunology of the disease, viral persistence, vascular issues, blood clotting, pathogenesis specific to the central nervous system, and pathogenesis of Long COVID in children. It also fostered discussions on how the current understandings of pathobiology can better inform clinical trials.

“We all agreed that there was uncontrolled viral replication and an inflammatory immune response during acute COVID that seems to be associated with Long COVID,” Spudich said, about one consensus from the workshop. 

The group agreed that there is evidence of spike protein RNA and other parts of the SARS-CoV-2 virus in some infected people, particularly those who got sick during early waves. Still, she said the group agreed “that viral persistence does not seem to explain Long COVID in all patients.”

Spudich also gave a summary of the workshop’s talk on immune dysregulation following SARS-C0V-2 infection.  “Simply having had COVID has altered our immune signatures in many, many people,” she said. Because of this, she said that when studying Long COVID it is important to compare people with the disease to not only people who did not have COVID-19, but also people who have “fully recovered.”

The Yale workshop group also talked about the importance of conducting more pathobiology studies in children with Long COVID, as well as fostering more collaboration between researchers. There is a strong need to continue prospective longitudinal cohorts (e.g. studying people over a long time) “in tandem” with clinical trials, she said, with special attention to adaptive platform trials testing multiple interventions.

Finally, Spudich pointed out that there are approved treatments for other conditions that lack widely accepted biomarkers, including migraines, and that this may be one route the community can use to better convince pharma to invest more in Long COVID.

— Miles Griffis

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12:30 p.m. ET: A note on access

Despite attendance from many Long COVID community members both in person and virtually — and despite taking place amid a COVID-19 surge in the U.S. — the RECOVER-TLC workshop has not prioritized acute COVID-19 precautions, some attendees told The Sick Times during Wednesday’s lunch break.

The workshop has not required high-quality masks, distinct from other Long COVID events such as last month’s Keystone Symposia meeting. Some NIH staff and speakers have worn masks, but taken them off to deliver presentations. Meeting staff also made KN95s available to attendees. One advocate at the meeting in person observed that an attendee behind her was loudly coughing without a mask on.

In addition, the meeting space has not provided any outdoor seating options during meals, leaving attendees seeking to avoid SARS-CoV-2 reinfections to eat sitting on the ground and sharing a single bench outside the hotel’s main entrance.

Last year’s RECOVER-TLC workshop similarly drew criticism from Long COVID community members for not requiring masking, which one advocate called a “microaggression,” along with access issues with that event’s livestream. 

— Betsy Ladyzhets

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12:30 – 1:00 p.m. ET: Discussion on Clinical Trial Design

After the lunch break, NIAID biostatistician C. Jason Liang presented on clinical trial design. While Liang has advised RECOVER-TLC on its designs for upcoming clinical trials, his talk at the workshop did not discuss specific aspects of those studies but rather shared different issues that he recommends researchers consider when designing trials.

Liang’s talk focused on platform trials, trials that test multiple treatments at once and often evolve as they go. These trials can be more efficient than testing each treatment in its own trial, Liang said, but they also take longer to operate and can get quite complicated.

He discussed examples from Ebola and acute COVID-19 research. In an Ebola platform trial, called PALM1, researchers started with two drugs and a placebo, then added another drug, then increased the sample size. In an acute COVID-19 platform trial, called ACTT, researchers started by studying remdesivir (an antiviral that became a major COVID-19 treatment) and a placebo, then shifted to comparing remdesivir by itself to remdesivir in combination with other drugs.

Platform trials are “all different in their own ways and highly dependent on the context” in which those trials are started and run, Liang said. He shared several issues that researchers might consider when designing these trials: tradeoffs between trying more treatments at once and trial cost; ensuring that treatments in a platform trial can be studied with the same endpoints; how to keep participants and researchers blinded; challenges with statistical analysis; and maintaining control groups throughout the study that can be compared to treatment arms.

Liang also advised against a practice called response-adaptive randomization, in which researchers adapt their trials by reducing the number of participants who receive a control or less effective treatments, in favor of giving more participants a more effective treatment. This practice gets people to treatment more quickly, but can lead to statistical challenges in completing the study and interpreting results, Liang said.

During the session’s Q&A, Liang encouraged researchers to collaborate with biostatisticians like him when designing trials, to think through these issues before taking steps like applying for FDA authorization.

— Betsy Ladyzhets

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1:00 – 2:25 p.m. ET: Additional Gaps to be Filled by RECOVER-TLC

Next, the workshop hosted a panel discussion on additional gaps in Long COVID research that RECOVER-TLC might fill. The panel was moderated by Sally Hodder from the West Virginia University School of Medicine, and included panelists Amy Proal of PolyBio, who joined virtually, Alexandra Yonts of the Children’s National Hospital, Tess Falor of Renegade Research, and Gustavo Kijak from AstraZeneca.

Proal stated that the biggest intervention missing from RECOVER-TLC was a mechanistic trial of a “highly potent, broad-spectrum, very up-to-date monoclonal antibody,” referencing David Putrino’s presentation this morning about SPEAR’s proposal for a trial with VYD2311. Meanwhile, Yonts advocated for including children in all of the RECOVER-TLC trials, stating that failing to do so “creates unnecessary delay.” 

Falor brought up several issues: she mentioned a need for trials to identify which participants have other infection-associated chronic conditions — drawing attention to a recent letter by several advocacy groups and research centers. She also said that some social media comments about the meeting criticized it for “mildwashing,” or not including people with the most severe presentations of the disease. She also pointed out there were not any presentations or consideration on “Long Vax,” also called post-COVID vaccine syndrome, which some leading Long COVID researchers are studying.

Kijak from AstraZeneca, speaking with the caveat that he is on the panel expressing his own opinions and not those of the company, said that it was important to allocate funds for follow-up analyses after trials wrap, so that each trial can be a stepping stone to the next.

The moderator then invited the audience to share gaps that they saw in RECOVER-TLC. 

Some questions centered around biomarkers; Proal spoke about how programs like VIPER, the collaborative biomarker initiative, could help future clinical trials. 

Another commenter proposed a public review period for trials, which would make the process more “democratic,” allowing the community to comment more on trials before they begin. Beigel responded that more community comments are always better. “We should make a commitment that we will exceed prior levels of public engagement,” he said, but he was not sure exactly what that looks like.

Other questions and issues centered around medical education — asking how RECOVER might help inform physicians about the latest Long COVID research, as patients and caregivers are often dismissed when they bring scientific papers to appointments — endpoints for trials, reinfections, whether genetics play a part in Long COVID, subgrouping, and further inclusion of people with ME in RECOVER. “Please take care of my ME/CFS patients too,” researcher Nancy Klimas said in a comment. 

Closing out the Q&A, Meighan Stone of the Long COVID Campaign (referencing yesterday’s story in The Sick Times about RECOVER-TLC’s trials announcement), asked for the NIH to be more transparent about their funding and timelines. “Help us help you,” she said, stating that more clarity would help advocates ask for more funding and to be strategic about prioritizing the resources that RECOVER does have.

Beigel also discussed RECOVER-TLC’s patient engagement process during an interview yesterday afternoon with Betsy. FNIH and NIAID received many applications from people interested in participating in working groups, he said, and TLC staff organized some of those applicants into groups based on their expertise. 

The final working groups included several focused on drug categories (antivirals, immunomodulatory, metabolic, neurologic, cardiovascular) and several focused on other interventions (devices, manual and physical therapies, nutrition and diet, complementary and integrative health). Beigel did not share specific details about how the staff narrowed down the applicant pool.

Some working group members and speakers at the meeting had originally submitted treatments for consideration, Beigel said, naming Anna Maria Bombardieri from Stanford (who spoke about stellate ganglion blocks) as one example. Beigel also noted that the working groups, while representative of people with Long COVID as well as researchers and clinicians, only include a small subset of community members — this week’s workshop is crucial for getting more public feedback, he said.

RECOVER-TLC “could have gone faster” but chose to take more time in order to consider trials with “full engagement” of people with Long COVID and clinicians, Beigel said during the interview, responding to critiques that the initiative should be approaching trials more urgently.

— Miles Griffis & Betsy Ladyzhets

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2:25 – 3:00 p.m. ET: RECOVER-TLC Next Steps and How to Proceed

In the last session of the workshop, co-chairs NIAID’s Joseph Breen and Upinder Singh of the University of Iowa Carver College of Medicine recapped comments and discussions they had heard throughout the event.

Singh, who shared that there was a “lot more” stakeholder engagement compared to last year, added that the question of biomarkers was prominent throughout the workshop. 

Both doctors referenced the ongoing conversation about building confidence and trust: “It has to be bilateral,” Singh said. “It’s not simply that patients should trust their providers, that patients should trust NIH, that patients should trust FNIH. … It’s kind of like asking everyone to accept that we’re in it together. And we are in it together.” 

Breen, in a separate conversation with The Sick Times, said RECOVER-TLC will be resuming its bimonthly webinars for regular updates. They had previous webinars in November 2024 and January 2025, but stopped after Trump assumed office. 

During the last session, Breen added that as RECOVER-TLC moves forward with the trials discussed during Day One of the workshop, they will make a projection about further trials “as quickly as possible and share that.” He then thanked everyone who helped the meeting happen, from its organizing committee to FNIH, NIAID, and NIH, then closed the second and final day of the workshop.

– James Salanga

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Editor’s note: PLRC, like The Sick Times, has received support from the Balvi and Kanro funds. Our newsroom operates independently of financial supporters.

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