Six Years In: The Present (Part 2 of 3)

Bridging the Treatment Gap

Today is the 4th International Long COVID Awareness day. Exactly 6 years and 2 days ago, the United States declared a shutdown. Something that was meant to be temporary, has lasted a lifetime for so many people. There are still people known as first wavers experiencing persistent symptoms from post-COVID. Today, we honor those who continue to fight, those we have lost to the disease, and the ongoing research to help people move forward once and for all. We do this by discussing the recent research that has helped us bridge the gap towards treatment.

This is Part 2 of a three-part series for Long COVID Awareness Month. If you missed Part 1, you can find it here.

Bridging the Treatment Gap

Structured Pacing (2022)

The strongest rehabilitation evidence to date comes from structured pacing research. A 2022 University of Leeds study published in the Journal of Medical Virology found that before entering a structured pacing program, participants were averaging three post-exertional crashes per week. After six weeks of weekly phone check-ins with a physical therapist guiding their pacing strategy, their crashes dropped to one per week. They also reported measurable improvements in activity levels, quality of life, and the three symptoms participants reported suffering most: fatigue, breathlessness, and headaches. The 2025 PACELOC study replicated and extended these findings, confirming that post-exertional symptom exacerbation can be meaningfully reduced through structured, individualized pacing rehabilitation. While rest is important, these studies support that methodically balanced rest and activity builds capacity without triggering collapse. What this reminds us is that improvement doesn’t solely belong to Big Pharma and medication management. Improving your quality through lifestyle changes can have a meaningful impact, and it is precisely the framework that guides how I coach people.

Stellate Ganglion Block (2024)

Stellate ganglion block (SGB), a nerve block targeting the autonomic nervous system, has emerged as one of the more intriguing interventional approaches for Long COVID. I get asked about this a lot. A 2024 retrospective analysis of 33 Long COVID patients found that most reported meaningful symptom relief within 24 hours of the procedure, with about one-third sustaining that improvement at the one-month mark. Relief was most consistent across fatigue, brain fog, and autonomic symptoms including exercise intolerance. The evidence is still early, but it is compelling enough that the NIH RECOVER program has selected SGB as one of only four treatments currently undergoing formal trial under its RECOVER-TLC initiative. That selection alone is meaningful: it signals that the research community considers this approach worth rigorously testing.

LISTEN Trial (2025)

The 2025 LISTEN trial, published in BMJ Medicine, reinforced a principle that rehabilitation clinicians have long held: that individualized, multidisciplinary care delivered in the community and in patients’ own homes produces better outcomes than one-size-fits-all approaches. The trial’s findings emphasized not just symptom management but functional improvement and return to pre-infection vocational levels, framing personalized rehabilitation as the current best-evidence standard for Long COVID care. This is not a drug trial. It is a study about the model of care itself, and what it tells us is that who delivers your care, how they deliver it, and whether it adapts to you as an individual matters enormously. The thing that I like the most about this study is that it de-emphasizes having to go to a clinic for care, something I feel strongly about. Because of the energy cost in Long COVID, I strongly believe that treatment should be delivered primarily in-home (whether that be virtual or a mix of in-person and virtual). Virtual eliminates access barriers and so many other risks associated with the condition like PEM crash from travel/stimulating environments, risk of reinfection, and many more.

Medications: A Piece of the Puzzle

Beyond rehabilitation, several pharmacological approaches are generating optimism. Some of them being low-dose naltrexone, rapamycin, and monoclonal antibodies (not an exclusive list). Low-dose naltrexone (LDN), an anti-inflammatory, immune-modulating drug used off-label for chronic neuroimmune conditions, has accumulated observational evidence suggesting moderate reductions in fatigue, brain fog, and sleep disturbances in a subset of Long COVID patients. Rapamycin, an mTOR inhibitor that may address T-cell exhaustion and the cell’s ability to breakdown and repair itself, is currently being trialed at both Simmaron Research and David Putrino’s CoRE clinic at Mount Sinai. Early reports show that roughly half of participants experience meaningful reductions in fatigue and post-exertional malaise. Additionally, the Putrino lab is running trials of antivirals and monoclonal antibodies targeting viral persistence, which is one of the hypotheses that the main driver of ongoing immune dysregulation is persistent viral remnants in the body. These are certainly promising studies, but it is important to note what the evidence actually shows: for most of these approaches, we are in early-trial or observational stages, and none yet constitutes a validated treatment. What the rehabilitation evidence offers that the pharmacological evidence does not offer yet is a body of replicated, peer-reviewed findings showing that structured lifestyle management can move the needle now, while the field catches up.

Recovery Statistics and the Phenotype Problem

When people ask about recovery from Long COVID, the honest answer is: it depends, and we are only beginning to understand what it depends on. The surface statistics offer some comfort. Most people who develop symptoms at four weeks recover by twelve weeks. However, for those still ill at twelve weeks, the trajectory shifts meaningfully. A 2025 RECOVER study tracking 3,659 participants over fifteen months found that 5% carried persistently high symptom burden throughout, 12% had non-resolving intermittently high burden, and 14% didn’t meet Long COVID criteria at three months but had increasing symptoms by fifteen months, which means that the illness doesn’t follow a predictable arc and doesn’t always make itself fully known early. It is variable across months and years, which is what makes the statistics so hard to track and interpret. Another piece of what makes these statistics so difficult to interpret is that Long COVID is not one disease. It has multiple phenotypes.

Research published across multiple journals, including a 2024 systematic review in eClinicalMedicine and the RECOVER program’s own 2024 subtype classification, has identified distinct clinical phenotypes: one dominated by smell and taste changes, another by chronic cough, another by brain fog, another by palpitations, and another by post-exertional malaise, dizziness, and GI symptoms. The problem with this phenotype classification is that it is by symptom. Dizziness can be triggered by dozens of different reasons. Chronic cough can be pulmonary or gastrointestinal related. Both of those have very different treatment pathways. This isn’t the only proposed phenotype classification. A 2024 study in BMJ Open Respiratory Research confirmed that these phenotypes differ not only in symptom profile but in lung function, disease severity, and likely underlying mechanisms.

Phenotype distinction matters enormously for how we interpret treatment research, and it is the central reason why so many intervention studies produce results that feel frustratingly inconclusive. When a clinical trial enrolls anyone with a Long COVID diagnosis and tests a single intervention, it is not testing apples against apples. It is as if they are testing apples, oranges, bananas, potatoes, leeks, and ground beef…and then averaging the results. A treatment that targets viral persistence may be transformative for the patient whose primary driver is a reservoir of lingering virus and irrelevant to the one whose symptoms are rooted in autonomic dysfunction. A pacing protocol that changes lives for someone with post-exertional malaise does nothing for someone whose main presentation is olfactory dysfunction. Generally speaking, when we look at the research, they aren’t proving treatments to have overwhelmingly high effective rates. They are finding modest effect sizes and mixed results, which is more a reflection of the failure to study Long COVID by phenotype as opposed to treatment failure. Think of it this way. It’s as if they are testing a new cancer treatment on people with brain cancer, breast cancer, colon cancer, and lung cancer instead of segmenting it to one specific cancer. Until trials begin matching interventions to phenotypes, we will continue having mediocre results. The field knows this. The push toward phenotype-specific trials is growing. And when those trials arrive, the picture of what actually works, and for whom, will almost certainly look very different.

To be clear, what I’ve just covered is a mere snapshot of the research. There are hundreds if not thousands of groundbreaking studies that have happened along the way. And while there are still many things to explore, we can confidently say that the culmination of research points towards Long COVID being a disease with multiple overlapping mechanisms. Those mechanisms include viral persistence in tissue reservoirs, immune dysregulation, T-cell exhaustion, autonomic dysfunction, gut-brain disruption, microclots, and now endothelial senescence. This is not a simple illness. It was never going to have a simple fix.

As it currently stands, the best approach is one that includes pacing, a multi-disciplinary team,a tailored approach and appropriate combination of medication management when lifestyle management isn’t enough.

As I like to say, there are over 600 different types of cancers, and that is exactly how we should be talking about Long COVID….and I think we are getting there.

For a field that didn’t exist in 2020, it now has nearly 10,000 published studies and is growing at 20% per year. That’s something to be extremely optimistic about. Despite its complexity, we have a map.

Coming Up on March 22nd

Part 3 is where we look ahead. I’ll be covering what is currently in clinical trials, what each intervention is targeting and why, and a full curated list of studies you can participate in right now. I’ve done the work of finding the links and eligibility details so you don’t have to.

And as always, if this resonates with someone you know, share it. Long COVID Awareness Month only works if the awareness actually spreads.

With love,
Dr. Meg

In honor of Long COVID Awareness Month I am offering a 30-day free trial to RAFT (Rise Above Fatigue Training), my self-paced course for Long COVID Management. This opportunity is available through March 31st. To learn more information about RAFT Essentials you can click here to receive more information and enroll.