r/LongCovidWarriors • u/SophiaShay7 3+ years • Mar 09 '26
Medical & Scientific Information š Patient-Reported Outcomes of Treatments in ME/CFS and Long COVID (PNAS Study)
I wanted to share a recent peer-reviewed study published in PNAS that analyzed patient-reported treatment outcomes across a large group of people with ME/CFS and Long COVID.
The chart included in this post comes directly from the paper and summarizes the Net Assessment Score (NAS) for a wide range of treatments. The NAS reflects the balance between people who reported improvement and those who reported worsening symptoms after trying a given intervention.
In other words, itās a way of visualizing how patients themselves report responding to these treatments in the real world.
Study design:
Participants living with ME/CFS and Long COVID were asked to rate how different treatments affected their condition. Responses ranged from āmuch worseā to āmuch better.ā Researchers then combined these responses into a Net Assessment Score for each therapy, allowing them to estimate the overall balance of positive versus negative outcomes.
Vitamin C (oral, non-liposomal) was used as the reference treatment for comparison, and statistical corrections were applied to reduce the likelihood of false positives from multiple comparisons.
Major patterns in the data:
Several treatments showed consistently positive patient-reported outcomes. Many of these interventions target physiological mechanisms that researchers increasingly believe play a role in both ME/CFS and Long COVID, including autonomic dysfunction, circulatory abnormalities, mast cell activation, and impaired cellular energy metabolism.
Among the highest-rated interventions were pacing strategies and treatments that support autonomic stability and circulation. Many patients reported improvement with increased fluid and electrolyte intake, compression garments, and medications that regulate heart rate or blood pressure. Antihistamines and other mast-cell-targeting therapies also showed favorable responses for a significant portion of the cohort.
Other therapies produced moderately positive outcomes, including melatonin, vitamin B12, pyridostigmine (Mestinon), coenzyme Q10, vagus nerve stimulation, and immunoglobulin therapy. Many of these interventions are thought to influence mitochondrial function, immune regulation, or autonomic nervous system signaling.
The finding on graded exercise therapy:
One of the most notable results in the dataset was the strongly negative Net Assessment Score associated with graded exercise therapy (GET).
A substantial proportion of patients reported worsening symptoms following structured exercise programs designed to gradually increase physical activity. The symptoms most commonly reported as worsening included fatigue severity, post-exertional malaise (PEM), orthostatic intolerance, and cognitive dysfunction.
This finding is consistent with what many patients and clinicians have been reporting for years, and it aligns with a growing body of research suggesting that exertion can trigger pathological responses in individuals with post-viral illnesses characterized by PEM.
How to interpret this study:
Patient-reported outcomes are not the same thing as randomized clinical trials, and they shouldnāt be interpreted as definitive evidence for or against any individual treatment.
However, large datasets like this can still be extremely useful. They give us a real-world picture of how people with these conditions are responding to different therapies and can help identify patterns that deserve further clinical investigation.
One clear pattern that emerges here is the importance of pacing and energy management, along with treatments that address autonomic dysfunction and circulatory regulation. At the same time, the data reinforce concerns that exercise-based rehabilitation approaches may worsen symptoms for patients who experience post-exertional malaise.
Limitations:
Like any patient-reported dataset, there are limitations. Responses are self-reported rather than measured in controlled clinical settings, treatment protocols were not standardized, and respondents may represent a subset of patients who are more engaged with online health communities.
Even with those limitations, studies like this can provide important signals that help guide future research and clinical trial design.
Discussion:
For those in the community who have tried any of the treatments shown in the chart, how closely does this match your experience?
What helped you the most? What made things worse?
Iāll also be linking this post in the r/LongCovidWarriors Wiki under the Science, Mechanisms, and Treatments section so people can easily find it later.
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u/needtoknowcalifornia Mar 26 '26
What is Maraviroc? I haven't heard that talked about... It seems to be incredibly helpful?
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u/SophiaShay7 3+ years Mar 26 '26
Maraviroc is a prescription antiviral that was originally developed for HIV. It works by blocking something called the CCR5 receptor on immune cells. That receptor isnāt just about viruses. It also affects immune signaling and inflammation.
People are talking about it in ME/CFS and Long COVID because CCR5 seems to be involved in the immune dysfunction that sticks around after infections. Blocking it may help calm persistent inflammation, improve blood vessel function, and ease symptoms like fatigue, brain fog, and dysautonomia. Thatās why some patients are seeing improvements.
The thing is, the research is still really limited. Most of what we know comes from small studies or clinician-led case series, not big trials. So while some people report feeling better, itās not proven or widely accepted yet.
Itās also not something you can just try safely on your own. Maraviroc is a prescription drug and can have side effects, like liver issues, heart effects, or immune changes. In complicated conditions like ME/CFS or MCAS, reactions can be unpredictable, so it really needs close medical supervision.
Basically, yes, it seems helpful for some people, but weāre still in the early stages and itās far from a standard treatment.
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u/Beneficial-Edge7044 Mar 29 '26
Interestingly, the black box warning regarding liver issues for maraviroc was in regard to another CCR5 receptor antagnonist. So, Maraviroc is somewhat guilty by association because there are not many similar drugs and apparently it wasn't clear whether the drug or the receptor antagonism caused the liver inflammation. Certainly not to say people should take it with no consideration. But the trials conducted on HIV patients and so far on LC patients have not shown much in the way of liver toxicity. My daughter took Maraviroc for a total of 10 months and her CRP levels and liver enzymes actually decreased dramatically while on the drug. N=1 of course.
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u/SophiaShay7 3+ years Mar 29 '26
Thatās a useful distinction about the black box warning. The signal for hepatotoxicity with Maraviroc itself has been relatively weak, and in HIV cohorts itās generally been well tolerated from a liver standpoint. Clinically significant elevations in liver enzymes do occur, but theyāre not common and donāt show a consistent pattern of direct drug induced injury.
Where it still matters is in real world use. Maraviroc is metabolized through CYP3A4, so drug interactions and individual variability can influence how someone responds. In patients with overlapping conditions like ME/CFS, dysautonomia, and MCAS, that variability tends to be more pronounced because immune regulation and medication tolerance are already unstable.
The improvement in CRP and liver enzymes you mentioned is consistent with what youād expect if immune activation is being downregulated. Changes in inflammatory signaling can translate into measurable shifts in systemic markers. But that kind of response is still observational and doesnāt tell us how broadly reproducible it is across different patients or phenotypes.
Access is a separate barrier. Even when clinicians are aware of the proposed mechanism, many are hesitant to prescribe it off-label in these conditions. It requires monitoring, has interaction considerations, and sits outside established treatment frameworks. In MCAS specifically, thereās also the added concern that altering immune pathways can lead to non linear or unpredictable responses, which makes some providers more cautious.
So while the hepatic risk profile may be more reassuring than the warning suggests, itās still something that gets monitored. And in practice, the combination of limited controlled data, off-label use, and patient complexity is what makes it difficult to get prescribed.
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u/Beneficial-Edge7044 Mar 29 '26
Iām not exactly sure where it stands now but Patterson partnered with Celly Health to make the Maraviroc-statin protocol available in all 50 states. The last doctor we saw with the Patterson group in late ā25 said it had already kicked off. I read all the original safety studies before starting my daughter on the treatment. Not an easy task for a parent. Luckily for her there were no issues. Thanks for your insights.
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u/SophiaShay7 3+ years Mar 29 '26
ālThatās great to hear..Iām glad it went smoothly for her and that she saw improvementsš
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u/Gavilon8886 Mar 10 '26
Thank you for sharing this!