What We’re Learning About Long COVID: Updates from the PNW RECOVER Town Hall

The Pacific Northwest RECOVER (PNW RECOVER) hub — led by the Institute for Systems Biology (ISB) with clinical partners UW Medicine, Providence, Swedish, and Cedars-Sinai — is part of a nationwide effort to understand, define, and ultimately treat long COVID.

At a virtual town hall held on November 17, 2025, ISB President Dr. Jim Heath joined clinical co-principal investigators Dr. Helen Chu (UW Medicine) and Dr. Jason Goldman (Swedish/Providence) to share what the national RECOVER 1.0 study has uncovered so far, where the science is headed next, and how upcoming clinical trials aim to translate biology into better care.

Mapping Long COVID Trajectories in RECOVER 1.0

Heath opened the program by describing the unprecedented scale of RECOVER 1.0. Over roughly four years, 15,156 participants were enrolled across 84 rural and urban sites in most U.S. states and Puerto Rico, contributing more than 160,000 blood draws and an average of 10.6 study visits per participant. That intensive follow-up has allowed researchers to carefully document the epidemiology and symptom patterns of long COVID.

Using symptom data from thousands of participants, Heath highlighted several “trajectories” — different ways symptoms can evolve after an initial SARS-CoV-2 infection. Some people experience persistent, high-burden symptoms that clearly meet long COVID definitions. Others fall just below that threshold, slowly improve over time, or develop new symptoms months after infection. These evolving trajectories, he noted, helped justify RECOVER 2.0, a next phase designed to follow a subset of participants over a longer period.

Heath also described how RECOVER is now pairing these clinical trajectories with deep molecular data. Whole-genome sequencing and large-scale blood protein measurements are underway, enabling researchers to explore polygenic risk scores (many small genetic variants acting together), viral reservoirs, and blood-based biomarkers that may distinguish different long COVID trajectories. RECOVER 2.0, scheduled to launch in May 2026, will re-engage roughly one-third of RECOVER participants with additional blood draws and questionnaires to extend these analyses over time.

What early clinical trials are telling us

Next, Chu reviewed what RECOVER and other studies have learned so far from long COVID clinical trials. She began with several leading hypotheses for long COVID mechanisms — viral persistence, microclots and organ injury, and dysregulated immune responses — and noted that early antiviral treatment during acute COVID has been associated with lower long COVID risk in multiple studies.

Two small randomized trials at Yale and Stanford tested whether Paxlovid (nirmatrelvir/ritonavir) could treat existing long COVID symptoms. In both studies, roughly 100 participants received either Paxlovid or a placebo for 15 days and were followed for changes in symptom scores. Neither trial showed a significant benefit compared to placebo.

Within RECOVER, the RECOVER-VITAL trial is evaluating longer Paxlovid courses in several arms, with participants followed for six months and biological samples collected to look for signals of viral persistence. Results are still being analyzed.

Chu also summarized results from RECOVER-NEURO, which tested three interventions for people with cognitive symptoms — online brain training, cognitive rehabilitation, and transcranial magnetic stimulation — against two placebo-style comparison groups. Across all arms, participants showed some improvement, but there were no meaningful differences between active interventions and the comparison groups.

The next wave of long COVID trials

Goldman then turned to what is coming next in the clinical trials landscape. A recent review of clinicaltrials.gov identified 133 interventional studies for long COVID in phases one through four, testing antivirals, immunomodulators, neuroactive therapies, cardiometabolic agents, and more. Some early trials, including a monoclonal antibody study, have not shown benefit, but they have yielded valuable biological data.

Within the RECOVER-TLC (Treating Long COVID) program, four new interventions have been prioritized for upcoming national trials: low-dose naltrexone, the immunomodulatory drug baricitinib, stellate ganglion block procedures, and GLP-1 receptor agonists (a class already used for diabetes and weight management). Goldman highlighted two trials that Swedish plans to offer locally: REVERSE-LC, which will test baricitinib in 550 participants with fatigue and brain fog, and ADDRESS-LC, which will evaluate an investigational neuroactive agent called Bezisterim in 208 participants with neurocognitive symptoms.

Goldman emphasized that these trials are being designed with extensive input from people living with long COVID and patient advocacy groups, and that “under-the-hood” biological measurements — such as immune cell profiling — are crucial even when symptom outcomes are modest. Just as combination therapy transformed HIV treatment, he noted, partial signals from early trials may ultimately point toward more effective multi-drug or multi-modal strategies.

Q&A: Risk factors, symptoms and what comes next

During the Q&A, the panel addressed questions on who is at risk for long COVID, why some people never develop it, and how RECOVER 2.0 will be structured. Age, pre-existing conditions such as diabetes or heart and lung disease, female sex, and lack of vaccination or hybrid immunity were discussed as established risk factors, though many underlying mechanisms remain unclear. The most common long COVID symptom clusters continue to include fatigue, brain fog, shortness of breath, and autonomic symptoms such as lightheadedness or palpitations.

The panel also reassured attendees that prior participation in RECOVER 1.0 generally does not exclude them from future clinical trials — and in fact, their existing longitudinal data make them especially valuable to researchers. RECOVER 2.0 will be smaller and more focused, enriching for participants who still have symptoms while tying long-term clinical follow-up to ongoing molecular and genetic studies.

You can watch the event in full here or by playing the video at the top of this page.