Despite launching with promises of urgency in fall 2024, the National Institutes of Health’s initiative has yet to start enrolling participants in new trials.
Leading Long COVID scientists, government officials, and advocates are meeting today and tomorrow in Bethesda, Maryland for the third annual RECOVER-Treating Long COVID (TLC) workshop, hosted by the National Institutes of Health (NIH) and Foundation for the National Institutes of Health (FNIH). At a hotel near the NIH campus, attendees will hear updates on the RECOVER-TLC program’s clinical trials as well as results from other recent studies advancing our understanding of the debilitating disease.
In September 2025, the second iteration of this meeting announced RECOVER-TLC’s three new clinical trials, which will study low-dose naltrexone in children and young adults, the GLP-1 drug semaglutide, and stellate ganglion blocks. Over a year later, these three trials have yet to start recruiting participants. Another trial, studying the JAK inhibitor baricitinib, had already started prior to RECOVER-TLC but was able to expand its recruitment to more trial sites because of the program’s support.
People with Long COVID and researchers outside the RECOVER program have long criticized the NIH for moving slowly toward clinical trials. The program allocated much of its original $1.15 billion in funding to observational research and initially failed to build on prior research in other infection-associated chronic conditions that overlap with Long COVID, like myalgic encephalomyelitis (ME). The NIH launched RECOVER-TLC in 2024 with promises to move with more urgency and quickly fund additional trials, but some of its newer efforts have garnered similar feedback.
In addition to updates on the RECOVER trials and opportunities for attendees to share feedback with the NIH and FNIH, the workshop’s agenda includes sessions on designing clinical trials, patient-reported outcome measures, the underlying biology of Long COVID, and results from other recent trials outside the NIH program.
As we do for all NIH RECOVER efforts, The Sick Times is closely following this workshop. I am attending the event in person in Bethesda while Miles Griffis and Heather Hogan watch virtually. Check this article throughout the two-day event to find our summaries of each session, and look out for additional updates on our social media pages.
— Betsy Ladyzhets, 9:30 a.m. ET
Wednesday, 9:30 – 10:00 a.m. ET: Welcome and Opening Remarks
In introductions to the event, NIH officials highlighted how people with Long COVID have informed the RECOVER-TLC initiative, through submitting proposals for treatments that they would like to see studied, serving on advisory committees, and sharing feedback on how to design clinical trials.
“I want to speak directly to the people living with Long COVID and to the clinicians and caregivers, all of whom confront the effects of this illness every day,” said NIH director Jay Bhattacharya, delivering opening remarks in-person this year. “The NIH remains committed to finding answers and advancing the safe and effective treatments for Long COVID.”
Bhattacharya said he has spoken to many people with Long COVID, including people serving in Congress and in other “high walks of life,” adding: “Long COVID can hit anybody, and it is absolutely devastating.” The NIH is “committed to making sure that we get excellent science,” he said, “and the RECOVER-TLC program is, to me, our flagship effort to find answers for Long COVID patients.”
New clinical trials “plan to launch in the coming weeks,” Bhattacharya said. He also noted that RECOVER-TLC’s trials could lead to new insights for other infection-associated chronic conditions, specifically naming ME and chronic symptoms after Lyme disease.
Workshop co-chair Joseph Breen, from the National Institute of Allergy and Infectious Diseases (NIAID), similarly said that RECOVER-TLC leadership has “always tried to make [the program] patient-centered and really develop protocols that could be useful to the community.” A key goal for this week’s event is sharing updates with “patient partners” and gathering input to continue making the “best decisions,” he said.
The RECOVER-TLC portal for treatment proposals has received over 600 submissions since it opened in 2024, including about 400 distinct intervention ideas, said Elizabeth Geerling, project manager from FNIH. Working groups within the initiative reviewed all of these potential treatments based on the experiences of people in the Long COVID community, scientific rationale, safety, feasibility for a large trial, and the ability to access the treatments after the study concludes, she explained. The portal is still open and considers additional submissions on a rolling basis.
Along with input from people with Long COVID, RECOVER-TLC has taken lessons from earlier work in the larger RECOVER program, including its observational research, studies into the disease’s underlying biology, and the first round of clinical trials, which started in 2023 and began to share results this year.
— Betsy Ladyzhets, 10 a.m. ET
Wednesday, 10:30 – 11:30 a.m. ET: Current Agents and Trials
Introducing a session about the four clinical trials supported by RECOVER-TLC, Seema Nayak, a clinical researcher at NIAID, noted how difficult it has been to design these studies. “Long COVID has challenged many of our traditional assumptions about post-viral illness, recovery, and clinical trial design,” she said. “It’s a complex, heterogenous condition that affects multiple organ systems, presents with a wide range of symptoms, and places a substantial burden on patients and families.”
And yet, Nayak added, people with Long COVID urgently need trials: “The search for effective treatment is not abstract; it’s immediate, it’s personal, and it’s long overdue.”
Nayak described how RECOVER-TLC’s process for designing its new clinical trials has been distinct from the prior trials in what researchers call “RECOVER 1.0.” “The approach has been different,” she said, particularly with more involvement from people with lived experience and other relevant expertise. For example, the working group for the LDN trial includes “a pharmacologist whose entire career has been focused on naltrexone for off-label clinic use,” she said. These working groups have had many meetings to discuss study plans, including over 50 each for the low-dose naltrexone and stellate ganglion block studies.
Brave-LC: Low-dose naltrexone
Laura Malone, a clinician who treats children with Long COVID at the Kennedy Krieger Institute, presented on the low-dose naltrexone (LDN) trial. Unlike other prior studies that have tested LDN for Long COVID, this study will focus specifically on children and young adults, including an age range of six to 25 years.
Explaining why RECOVER-TLC chose to study LDN for this pediatric trial, Malone explained that the drug may be able to reduce inflammation in the brain and activity of microglia, immune cells that live in the central nervous system, which may be a driver of neurological symptoms in Long COVID. There’s evidence from prior studies and from the patient community that this drug can help improve symptoms, but prior studies have primarily been small and included only adults, Malone said.
“It was imperative to the working group to make sure that LDN was safe for pediatric and young adult populations,” Malone said. Naltrexone is approved by the Food and Drug Administration (FDA) and has extensive safety data in the larger doses used for treating opioid addictions, she explained.
She hopes that “this type of study will then facilitate licensure of low-dose naltrexone and improve access and safety to it for a more widespread use across the United States for pediatric populations.” In the study, participants will take LDN via pills that have been manufactured specifically for the trial.
The Brave-LC trial will focus on reducing fatigue. It will test LDN over a period of 16 weeks and will include 1,300 participants across 158 study sites, making it by far the largest pediatric Long COVID trial so far. Along with fatigue, the researchers will measure “overall quality of life, physical and psychosocial functioning, pain,” and some cognitive outcomes, Malone said.
Participants will be eligible to participate if they have fatigue and at least one other symptom that started after a COVID-19 case and lasted for over three months, Malone said. A positive SARS-CoV-2 test is not required, she noted. This study, along with other RECOVER-TLC trials, is using the 2024 National Academies of Sciences, Engineering, and Medicine (NASEM) definition of Long COVID to inform its eligibility criteria.
The trial will include three in-person study visits and six remote visits, over the course of six and a half months. Researchers designed the trial to “try and limit the need for in-person visits as much as possible while maintaining the efficacy and also the safety of the trial,” Malone said. At the in-person visits, participants will have their blood sampled so that researchers can look at pharmacokinetics and biomarkers.
The trial will likely start recruiting participants in the coming weeks, Malone said. The FDA has designed the study as “safe to proceed” and it received initial institutional review board (IRB) approval, though some late changes to the protocol are going through IRB review. “The goal is to activate the first site sometime mid-November,” she said.
In a Q&A segment, attendees asked questions about the trial’s endpoints and dosing strategy, as well as about a recent preprint on a Canadian trial for LDN that found the drug was not effective compared to placebo for people diagnosed with ME triggered by a SARS-CoV-2 infection. That trial assessed the drug in adults and was a much smaller study than BRAVE-LC plans to be. Malone said Brave-LC, with a larger cohort, will do a subgroup analysis among a more diverse group of participants, and noted she and her colleagues are in communication with the Canadian group about their findings.
To conclude discussion of this trial, pediatrician and RECOVER researcher Melissa Stockwell shared comments from two children with Long COVID, which had been sent to the advocacy group Long Covid Families. One commenter, age 17, said: “Just the idea that children were being included in research brought me so much hope. … We need more than just temporary fixes and symptom relief. We need treatments for chronic fatigue, autonomic dysfunction, and the countless other comorbid symptoms of Long COVID. Please keep fighting for a cure and for our future.”
A second commenter, age 9, shared: “I got Long COVID in kindergarten and have been sick ever since. … Please talk about how sick we are, and please find treatments for us.”
— Betsy Ladyzhets, 11:30 a.m. ET
Tame-LC: Semaglutide
Agam Rao from NIAID presented on semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1). Some people are using GLP-1s off-label for Long COVID and some are seeing improvements in their symptoms, Rao said. Semaglutide has a lot of established safety data from other prior studies. She also noted that semaglutide is “associated with less weight loss than dual agonists like tirzepatide,” which is being tested in a separate Long COVID trial at Scripps Research. “We didn’t want to have to limit this trial to people who were at higher BMIs,” Rao said.
This study will examine whether a six-month course of semaglutide, administered through subcutaneous injections once a week, improves overall quality of life for people with Long COVID ages 18 to 70. Its primary outcome will be the PROMIS 29+2 scale, with secondary outcomes looking at changes in fatigue, cognitive symptoms, and physical capacity. Along with studying adults, the trial will also have a smaller arm testing semaglutide in adolescents ages 12 to 17, using a different patient-reported outcome for this group because the PROMIS scale is not validated for this age group, Rao said.
Tame-LC will also be a larger trial and is designated as phase 2b, with a total of 774 participants across 75 sites: 642 adults and 132 adolescents. Trial participants will be randomized within both age groups and baseline BMIs, Rao said, with twice as many people receiving the drug compared to the placebo group.
Participants will start at doses of 0.25 milligrams per week for four weeks, then can titrate up. The study will examine different potential doses, including maximums of 1 milligrams per week, 1.7 milligrams per week, and 2.4 milligrams per week.
This study will include seven in-person visits and six remote visits across six months, where participants will complete surveys about their symptoms as well as physical and cognitive assessments, including an active stand test, six-minute walk test, hand grip strength tests. Researchers will also collect samples for biomarker testing; there’s a full list of biomarkers that RECOVER-TLC plans to test among all three of its trials on the FNIH website.
The Tame-LC team submitted its review package to the FDA on October 13, Rao said, and is “getting FDA comments as we speak and addressing them.” It’s also received approval from an institutional review board (IRB). “We are still hoping that our first site is activated in late December,” Rao said.
In the Q&A period, attendees asked about safety for the trial, including for participants who have gastrointestinal issues like gastroparesis. The researchers will closely track “whether people’s symptoms worsen,” and if anyone meets a pre-specified threshold for safety issues, they may stop taking semaglutide, Rao said.
Block-LC: Stellate ganglion block (SGB)
Anna Maria Bombardieri, an anesthesiologist at Stanford University, presented on the stellate ganglion block (SGB) trial. In an SGB, a physician injects anesthetic into a patient’s neck in order to temporarily block the sympathetic nervous system.
An overactivated sympathetic nervous system may be contributing to symptoms in some people with Long COVID and other chronic infectious diseases, Bombardieri explained. This raises the question: “Could we temporarily block the sympathetic system, and by doing this, help restore the autonomic balance and improve symptoms in patients with Long COVID?” Some small studies and case series have suggested that the procedure can help improve symptoms, but it has yet to be tested in a large clinical trial.
The Block-LC study will have 272 participants at 20 sites across the U.S., with 136 receiving a SGB and 136 receiving a sham procedure. Adults ages 18 to 65 will be eligible if they report at least six months of symptoms, a substantial reduction in their pre-Long COVID level of functioning, and at least two symptoms among fatigue, cognitive issues, orthostatic intolerance, post-exertional malaise.
This sham procedure will be a “sensory sham that will mimic the active procedure without the anesthetic,” Bombardieri explained. Researchers will use the same procedural steps and language with both groups of participants to preserve blinding.
“We spent many of our meetings talking about blinding,” Bombardieri said, when an attendee asked for more details about the sham procedure during the Q&A session. It would be difficult to fully blind participants without putting people in both groups under general anesthesia for up to 18 to 24 hours, she said, which is not feasible for a trial like this. The trial’s working group landed on the best method possible under the constraints they have, she said, and drew from past experience doing sham procedures in other trials. “We are confident that many people in the sham [group] will not be able to understand in which group they were assigned,” she said.
This study will include 12 visits across 26 weeks, including four visits for SGB procedures and then follow-ups to assess participants’ recovery and how much their symptoms improve. The primary outcome will be how much overall health-related quality of life changes from baseline to eight weeks, with secondary outcomes measuring fatigue, attention and memory, and a variety of other symptom changes, along with biomarkers.
After the initial, randomized phase of the trial, researchers will review the procedure’s safety and efficacy. If the initial results are favorable, they might pursue an open-label extension “where the patients who have received a sham injection have the opportunity, if they wish, to receive the blocks,” Bombadieri said.
Block-LC has received its IRB approval and is currently going through FDA review, Bombardieri said. The team hopes “that the first participant enrollment will happen in December of this year.”
REVERSE-LC: Baricitinib
Concluding the morning sessions, researcher Carolyn Bramante of the University of Minnesota gave a brief presentation about the REVERSE-LC trial, an ongoing study that received additional support from RECOVER-TLC last year. Of the RECOVER-TLC trials, it is currently the only one currently recruiting participants.
The study is assessing the drug baricitinib (Olumiant). Baricitinib is a JAK inhibitor, a class of drugs that suppresses the immune system. Many are currently approved by the FDA for various autoimmune disorders. Two other JAK inhibitor drugs, abrocitinib (Cibinqo) and upadacitinib (Rinvoq), are currently being trialed for Long COVID by other research groups.
“Enrollment now is going very quickly,” Bramante said, noting the study team has a goal of starting 35 participants in the randomization process a month. The study is also gathering extensive data at the start of the trial, six months, and twelve months, Bramante explained, including an optional cardiopulmonary test (CPET). So far, 328 participants have completed this test.
“We don’t have many people who have passed the 12-month mark yet, but that’ll be a great source of data for really understanding this disease,” Bramante said. She explained other opt-in tests within the trial, including lumbar punctures and tilt table tests, which will gather more information not only about baricitinib for Long COVID, but also the overall disease’s underlying biology.
With its many tests and check-ins, the study can be onerous for participants. One REVERSE-LC participant, Miranda DeNovo, said in the Q&A session that her first study visit took five hours. Others in the Q&A asked about participant compensation.
— Betsy Ladyzhets & Miles Griffis, 12:30 p.m. ET
