Open Problems in Long COVID and ME

As a community, we love to note all of the problems we face, but until now, there has never been a single, structured map of every open problem that quickly shows which people and organizations are working on them, and easily allows people with solutions and ideas to get involved!

Open a problem to see proposed solutions and who is already working on it, then sign up to join the effort.

How many patients have been told it is all in their head, handed a therapist's number, and sent home? The biopsychosocial model gave a generation of clinicians permission to stop looking. It is not a fringe view either: it is baked into guidelines, textbooks, and insurance policy. Dislodge it and almost everything else on this map gets easier.

Proposed solutions
  • Document and rebut biopsychosocial claims in the literature.
  • Train clinicians on post-viral disease.
  • Publicize the biomedical evidence base for a lay audience.
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Your GP is usually the first door you knock on, and too often it is the wrong door. Most doctors were taught almost nothing about post-viral disease, so they improvise, and the improvisation ranges from unhelpful to actively harmful. The knowledge exists; it just has not reached the people in the room with patients.

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This is the rare problem where doing nothing would be safer than what is prescribed. Graded exercise is still handed out despite years of patient-reported harm, and for people with post-exertional malaise, pushing through can mean losing function that never comes back. Getting it out of protocols and clinics is unfinished work.

Who is working on it
  • Tom KindlonAdvocate Long-running analysis of how harms are under-recorded in exercise trials. [link to verify]
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Call it "chronic fatigue syndrome" and people picture being a bit tired. Call it "myalgic encephalomyelitis" and people cannot pronounce it, spell it, or agree it is accurate. The disease is stuck between a name that trivializes it and one that confuses everyone, and no one has landed a replacement that is both accurate and usable.

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On this scale, "mild" can mean you can no longer work, socialize, or leave the house reliably. When the gentlest label already describes serious disability, the words quietly tell assessors, clinicians, and family that things are less bad than they really are.

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There is no lab slip you can put on the desk to end the argument. Without an accepted way to evidence the illness, every doctor's visit, benefits claim, and accommodation request starts from zero, and the patient carries the burden of proof for a disease that offers them almost no easy proof.

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Awareness sits upstream of almost everything: funding, volunteers, political will, a friend who actually believes you. Millions are affected, yet the disease barely registers in public life, and that silence is expensive in every direction.

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Search the illness and you get a woman resting her head on her hand, looking a little sleepy. That single stock photo does quiet damage, teaching everyone who sees it that this is ordinary tiredness rather than a life often spent in a darkened room.

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One famous person saying "I have this" can do more in a week than years of campaigning. Those disclosures are rare, partly because the illness hides people away, and partly because going public with it still carries a stigma of not being taken seriously.

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When a national body (NICE, CDC, IQWiG, NHMRC, Norway) opens a guideline for comment, someone has to be in the room. Too often no one coordinated is, and the committees that get seated can be stacked with conflicted or biased members. These processes decide care for millions and run largely unwatched.

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Winning a good guideline is only half the battle. The 2021 NICE guideline exists on paper, but implementation lags and there is steady pressure to water it down or reverse it. Defending a win takes as much work as securing one.

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A flawed review does not just fade away. The Cochrane exercise-therapy review keeps getting re-dated and republished, lending old, contested conclusions fresh authority. Someone has to track and challenge these zombie documents.

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If the disease is not coded correctly, it is invisible to health systems: no accurate counts, no billing, no research cohorts. ME is miscoded or missing across ICD-11, ICD-10-CM, SNOMED, and their national implementations.

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The psychological framing keeps rebranding. Somatic Symptom Disorder, Bodily Distress Disorder, MUS, Functional Neurological Disorder: each new label repackages the same assumption and pushes it into new specialties, quietly pulling patients back under a psychosomatic umbrella.

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Even patients who know exactly what they have often cannot find a doctor who does. The specialist workforce is tiny relative to millions of patients, so waitlists stretch for years and whole regions have no one at all.

Who is working on it
  • Doctors with ME Educates and organizes clinicians to grow a competent workforce.
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Patients trade doctor names in forum threads and DMs because no trustworthy, maintained directory exists. Finding safe care should not depend on luck and word of mouth.

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The sickest patients are the ones who physically cannot get to a clinic, yet phlebotomy, dental, and imaging are almost never brought to the home. Care is structured for people well enough to travel, which excludes exactly those who need it most.

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A hospital stay can make a severe patient permanently worse: bright lights, noise, no understanding of PEM, mishandled feeding and basic supportive care. There is no standard protocol staff can follow to avoid harm.

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A newly diagnosed patient faces a wall of scattered, contradictory advice at the exact moment good pacing decisions matter most. There is no trusted starting guide for the first weeks and months.

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Almost every other problem on this map gets easier the day there is a test. Yet there is no coordinated, funded push to develop and validate one, only scattered candidate biomarkers that never cross the finish line.

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Post-exertional malaise is the core feature of the disease, but the usual way to provoke and measure it can seriously harm patients. Trials and clinics need a safe, standard measure they do not currently have.

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Different studies use different definitions, so they are often not even studying the same patients. Without agreed criteria and subtypes, findings cannot be compared or combined, and trials lump unlike patients together.

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Every research team rebuilds from scratch because there is no shared backbone: no standing cohorts, registries, biobanks, or tissue and autopsy programs to draw on. Shared infrastructure would multiply the output of a small field.

Who is working on it
  • DecodeME Built a large patient cohort and DNA study, a model for shared infrastructure.
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Unblinded trials with subjective outcomes, poor harms recording, and appraisal tools (GRADE, risk-of-bias) that mishandle them have produced a distorted evidence base. Better methods and appraisal are prerequisites for trustworthy results.

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It took a 2016 tribunal to pry the PACE data loose. When reanalysis requires a legal fight, bad conclusions stand unchallenged for years. Routine, open data sharing should be the default.

Who is working on it
  • David Tuller Trial By Error reporting pressing for data release and reanalysis.
  • Brian Hughes Methodological critique of trial data and its reporting.
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There is no agreed charter setting PEM-inclusive criteria, genuine patient involvement, and no deficit framing as baseline expectations. A shared standard would keep new research from repeating old harms.

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Priorities get set without patients, researchers have little direct contact with them, and there are few registers matching willing patient representatives to the teams who need them. Involvement is treated as a formality, not a resource.

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A small field cannot afford to waste effort, yet teams work in silos and repeat each other without knowing it. There is no coordinating layer to align a shared agenda.

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The pipeline is thin: little funding, little prestige, and few mentors mean few new scientists choose this disease. Growing the next generation of researchers is its own distinct problem.

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Hard-won datasets and biological samples sit locked in individual labs. Without open sharing, the same collection burden falls on patients again and again, and reuse never happens.

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Some of the most promising candidates are cheap generics with no pharma backer, so no one pays for the trial. Off-patent does not mean off-limits, but the funding model treats it that way.

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Trials stall because eligible, willing patients are hard to reach and enroll, especially the housebound. Better recruitment infrastructure would speed every study in the field.

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The most affected patients are routinely designed out of trials because there is no scaled wearable or passive data collection and no infrastructure for decentralized, patient-led, or N-of-1 studies. The evidence base then ignores the people who need answers most.

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How often do we see a study with an interesting result, and then no follow up? There is basically no incentive or funding for Research Team B to replicate Research Team A's finding. PhDs want and need their own ideas to test; there is no credit, career advancement, or recognition for confirming someone else's.

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Most breakthrough fields have a handful of major donors who de-risk the early work. This one does not, so ambitious projects never get off the ground.

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Measured per patient or per year of life lost, public research funding for this disease is a fraction of comparable conditions. Closing that gap is a sustained political and budget fight.

Who is working on it
  • Solve M.E. Lobbies US agencies for research appropriations.
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There are no pooled funds, prizes, bounties, or microgrants to move small amounts of money quickly to promising people and ideas. The tooling that lets a community self-fund simply is not built.

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Other patient movements retain professional lobbyists who work legislatures full time. This field relies on exhausted volunteers, and it shows in the results.

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The organizations that do exist are often under-resourced and run by sick volunteers, limiting how much they can raise and deploy. Building real operational capacity is itself a problem to own.

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Competing national charities duplicate effort, governance is uneven, and cross-border fundraising loses tax relief. A fragmented sector wastes scarce money and goodwill.

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Drug companies do not see the size of the opportunity, so they stay away, which keeps the trials unfunded. Making the market legible could change the incentives.

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Pressure comes in bursts around awareness days and then fades. Lasting change needs steady, organized pressure that does not depend on a few people's remaining energy.

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The people with the most reason to protest are often the least able to show up. Advocacy tactics built for healthy bodies exclude the movement's own base, so new low-energy forms of action are needed.

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Documented harms from bad care and denied claims rarely reach a courtroom because no coordinated legal strategy exists. Litigation could both compensate patients and change institutional behavior.

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Government assessments measure quantity of output, not cognitive quality, and private insurers deny claims via "no objective proof" exclusions and social-media surveillance. The system is built to say no to exactly this disease.

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Severely ill adults can be sectioned on a psychiatric basis, and families have no prepared evidence pack to challenge it in the moment. A ready legal and medical defense kit could prevent real harm.

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Whether ME or Long COVID counts as a protected disability depends on where you live and who reviews your case. Inconsistent recognition means inconsistent access to accommodations and protection.

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Key records that would document neglect and harm are locked away in government files and clinic archives. Getting them released is slow, adversarial work that few are equipped to pursue.

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Not every gatekeeper is external. Some established organizations focus more on institutional survival and keeping members calm than on pushing hard for evidence-based change. Reforming or routing around them is delicate but real work.

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There is essentially no assisted, low-income, co-living, or community housing built around the needs of this disease: dark, quiet, low-exertion, with care on hand. Patients improvise in housing that actively works against them.

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There is nowhere to go for a supervised period of deep rest during a crash, and no respite to relieve exhausted caregivers. The care model has a gaping hole where these facilities should be.

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Standard shelters are loud, bright, and exertion-heavy, making them impossible for severe patients who lose housing. Illness and homelessness compound each other with no safety net in between.

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Partners and family become full-time carers with no training, pay, or respite, and relationships buckle under the load. Supporting caregivers is part of supporting patients.

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General crisis lines rarely understand the disease, and despair is common. A crisis and suicide-prevention resource built for this community, by people who get it, does not exist.

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For the most severe, unrelenting cases, the absence of legal, humane options is its own source of anguish. It is a hard, contested issue that the community nonetheless has to be able to discuss.

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The disease quietly removes people from work, friendships, and public life, and the loneliness compounds the illness. Rebuilding low-energy ways to stay connected is real, needed infrastructure.

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Meeting people and dating assume an energy and mobility budget patients do not have. There are no tools or spaces designed for finding connection within these constraints.

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Patients help each other constantly but informally. There are almost no durable structures (mutual-aid funds, unions, co-ops) to pool money and bargaining power at scale.

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Adjusting to a life-altering illness is real psychological work, distinct from the discredited idea that the disease is psychological. Few therapists are trained to help with that adjustment without stigma.

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The very people these services target often cannot use them: too much reading, light, motion, or clicking. Patient-facing tools need to be designed for fatigued, sensitive users first.

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What is worth trying, what is worth testing, and what is a waste of scarce energy and money? There is no maintained, trustworthy guide, so every patient reinvents the research.

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Thousands of recovery and treatment stories are scattered across forums in a form no one can learn from systematically. Structuring and validating that data could surface real signal.

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Desperation is a market, and it is being worked hard. Expensive, unproven cures drain patients financially and emotionally, and there is little organized pushback.

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Slick, well-funded programs dominate search results and feeds, often recycling the same psychological framing patients are trying to escape. Good information is being out-marketed.

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The good information that exists is spread across random social-media posts, buried and unverified. Without consolidation, patients cannot tell signal from noise.

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Disbelief from the people closest to you is one of the heaviest parts of the disease. Clear, shareable explanations that actually land with loved ones are in short supply.

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The most affected patients are too ill to advocate, attend, or even be photographed, so they vanish from the public picture of the disease. Their invisibility shapes how seriously everyone else takes it.

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EHCPs, tuition refunds, flexible deadlines, and virtual schooling are patchy or absent, so illness quietly ends educations. Systems built for full-time attendance cannot bend to fluctuating capacity.

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A majority-women disease has almost no guidance on how it interacts with cycles, pregnancy, and menopause. Patients navigate major hormonal transitions with no evidence to guide them.

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Sick children face disbelief, missed diagnoses, and even safeguarding accusations against parents. Pediatric care and research lag far behind even the thin adult provision.

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  • TYMES Trust Supports children and young people with ME and their families.
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The stereotype of the disease as a white, middle-class condition is a research and access failure, not a fact. Minorities are underdiagnosed, understudied, and underserved.

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People with vaccine-associated post-viral illness sit in a politically radioactive gap, wanted by neither side of the vaccine debate. The taboo leaves a real patient group without support or study.

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Most resources, research, and advocacy are concentrated in a few wealthy countries. Patients elsewhere lack local diagnosis, guidance, and organizations in their own language and system.

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