International experts publish consensus framework to standardize ME/CFS diagnosis

For decades, patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have navigated a medical landscape defined by uncertainty, waiting years for a diagnosis that often depends more on the clinician they happen to see than on any standardized set of measurements. Now an international consortium of nineteen multidisciplinary experts has taken one of the most consequential steps yet toward changing that, publishing a consensus framework in BMC Medicine that, for the first time, integrates measurable, risk-stratified assessments across seven core symptom domains into a single diagnostic roadmap for ME/CFS and the overlapping post-acute infection syndromes that include long COVID.

The work, led by Sławomir Kujawski of Nicolaus Copernicus University in Toruń, Poland, together with co-corresponding author Paweł Zalewski and an author team spanning institutions in Australia, Belgium, New Zealand, the United Kingdom, the United States, Latvia, Italy and Sweden, addresses a problem that has haunted the field since the illness first entered the medical literature. ME/CFS lacks validated objective diagnostic criteria. Patients routinely endure delays of years before receiving a diagnosis, and management varies so widely between clinics that two people with identical symptoms may receive entirely different evaluations and advice. The absence of standardization has also hampered research, making it difficult to compare findings across studies or to pool data in meaningful ways.

The consensus process itself was rigorous and transparent. Using a modified nominal group technique, a structured method designed to extract genuine agreement from panels of specialists rather than allowing dominant voices to set the agenda, the researchers guided the nineteen experts through successive rounds of discussion and anonymous voting. The participation rate across domains ranged from 89.5 to 100 percent, and agreement ranged from 94.7 to 100 percent, figures that speak to the depth of convergence the process achieved. Crucially, the panel included representatives of fields that rarely sit at the same table: exercise physiology, neurology, immunology, infectious disease, otorhinolaryngology, psychiatry, microbiology and molecular medicine, alongside contributions from patient advocacy networks including the ME Association UK, which provided structured feedback during the drafting phase.

The framework organizes the clinical picture of ME/CFS into seven core domains: post-exertional malaise, autonomic dysfunction, cognitive impairment, functional decline, sleep disturbances, pain and hypersensitivities. Post-exertional malaise, or PEM, is widely regarded as the hallmark symptom of the illness, a pathological worsening of symptoms following physical or cognitive exertion that would be trivially tolerated by healthy individuals. The framework defines provisional parameters for identifying and characterizing PEM, a step the authors say is essential because PEM is what most reliably distinguishes ME/CFS from ordinary fatigue and from fatiguing illnesses such as depression.

For each domain, the consensus group specified a battery of subjective and objective tools, with provisional cut-off values intended to guide interpretation. In the autonomic domain, for example, the framework draws on instruments such as the Composite Autonomic Symptom Score-31 (COMPASS-31), the Orthostatic Hypotension Questionnaire and the Orthostatic Grading Scale, paired with physiological testing including active standing tests and, where clinically indicated, head-up tilt testing to detect orthostatic hypotension and postural orthostatic tachycardia syndrome, both of which are common in ME/CFS. Cognitive impairment is assessed through validated instruments such as Addenbrooke’s Cognitive Examination-Revised and the Cognitive Failures Questionnaire, complementing the fatigue scales, including the Chalder Fatigue Questionnaire, the Fatigue Severity Scale and the DePaul Symptom Questionnaire in both its full and short forms.

The domain of exercise capacity introduces the most technically demanding element of the framework: cardiopulmonary exercise testing, or CPET. This is the gold-standard method for measuring how the body extracts and uses oxygen during graded exertion, and it provides objective indices such as the first ventilatory threshold, peak oxygen uptake and the respiratory exchange ratio at peak intensity. Two-day CPET protocols, in which patients repeat the test within twenty-four hours, have shown that people with ME/CFS often fail to reproduce their initial performance, an abnormality not seen in healthy controls or in most comparison populations. Hand grip strength and functional capacity questionnaires such as FUNCAP provide complementary, lower-burden measures of physical function. Pain and hypersensitivity are evaluated through pressure pain thresholds, the Widespread Pain Index and the Central Sensitization Inventory, reflecting growing evidence that central sensitization, an amplification of sensory processing in the nervous system, contributes to the widespread pain and sensory intolerance characteristic of the illness.

Sleep assessment completes the picture, drawing on the Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale and polysomnography where warranted, allowing clinicians to distinguish the unrefreshing, non-restorative sleep of ME/CFS from primary sleep disorders that require entirely different treatment. Functional decline, the domain that captures the real-world impact of the illness, is measured with instruments such as the Short Form-36 Health Survey and the Functional Capacity questionnaire, anchoring the entire evaluation in what patients can actually do day to day.

What distinguishes this framework from earlier attempts at standardization is its explicit safety-first architecture. The authors have designed a tiered, color-coded clinical pathway that prioritizes patient safety by escalating testing only when clinically essential. This design choice matters because several of the objective assessments used in ME/CFS research carry risks for this population. Prolonged upright tilt testing can provoke severe and prolonged symptom flares, and maximal exercise testing can trigger crashes that leave patients bedbound for days or weeks. By reserving the most provocative tests for cases where they are genuinely needed, the pathway reduces iatrogenic harm, an all-too-common feature of the ME/CFS clinical experience.

The authors are equally candid about the limitations of their work. Every threshold in the framework is provisional. None of the proposed cut-off values has yet been prospectively validated against fatigued disease controls, meaning that the comparisons that would demonstrate whether these measures truly separate ME/CFS from other causes of chronic fatigue remain to be conducted. For that reason, the consensus statement recommends that these measures currently support research standardization and cautious clinical exploration rather than definitive diagnosis. This is a framework for building the evidence base, not a final arbiter of who has the disease, and the authors emphasize that clinicians using it should interpret findings in light of the whole clinical picture.

Even with that caveat, the significance of the consensus is difficult to overstate. The COVID-19 pandemic has dramatically raised the stakes, as a substantial subset of people with long COVID develop a syndrome that is clinically indistinguishable from ME/CFS, complete with PEM, orthostatic intolerance and cognitive dysfunction. A standardized measurement framework applicable to both populations gives researchers a common language for the first time, enabling studies of post-acute infection syndromes to define their cohorts comparably, replicate one another’s findings and combine data across continents. The expert panel included researchers with deep experience in long COVID, such as Danilo Buonsenso of the Fondazione Policlinico Universitario A. Gemelli in Rome, ensuring the framework was built with the post-pandemic landscape in mind.

The consensus process also received no specific funding, a notable fact for an effort of this scale and an indication of the extent to which the field has been driven forward by researchers’ commitment rather than by major institutional investment. The published work, released as an open-access article, includes extensive supplementary material with appendices and tables detailing the provisional parameters for each tool, effectively handing clinics and research groups worldwide a practical toolkit they can begin adopting and testing immediately.

For patients, the framework’s most immediate promise lies in the prospect of shorter journeys to diagnosis. A clinician following the color-coded pathway can move systematically through the seven domains, using low-risk questionnaires and simple bedside measurements first, escalating only when the picture is unclear or when objective confirmation is essential for research participation, disability documentation or treatment decisions. This structured approach could reduce the diagnostic odyssey that currently averages many years and spare patients the dismissive encounters that have characterized so much of the ME/CFS experience.

The authors frame their contribution as pragmatic and foundational: a way of standardizing functional assessment so that the next generation of studies can be larger, more comparable and more reproducible. Prospective validation studies, which will test the provisional cut-offs against appropriate control groups, are the necessary next step, and the framework itself is designed to make such studies possible by specifying exactly which instruments to use and how to interpret them. If validation succeeds, the tentative thresholds of today could harden into the objective diagnostic criteria of tomorrow.

In a field where patients have long been told their illness is not measurable, the image of nineteen experts from nine countries converging on a shared set of measurable parameters across seven symptom domains represents more than a methodological advance. It is a signal that the biomedical era of ME/CFS and post-infectious chronic illness, accelerated by long COVID, has reached the point where standardization, validation and, ultimately, objective diagnosis are within reach.

Subject of Research: ME/CFS and overlapping post-acute infection syndromes; international expert consensus framework for standardized, measurable, risk-stratified diagnostic assessment across seven symptom domains

Subject of Research: Medicine

Article Title: Myalgic encephalomyelitis/chronic fatigue syndrome and overlapping post-acute infection syndromes: international expert consensus framework for diagnostic standardization

Article References: Kujawski, S., Eaton-Fitch, N., Słomko, J., Nijs, J., Polli, A., Hodges, L., Morten, K. J., Friedman, K. J., Hornig, M., Djalilian, H. R., Miglis, M. G., R. Godlewska, B., Prusty, B. K., Bonilla, H., Buonsenso, D., Tate, W., Murovska, M., Marshall-Gradisnik, S., & Zalewski, P. (2026). Myalgic encephalomyelitis/chronic fatigue syndrome and overlapping post-acute infection syndromes: international expert consensus framework for diagnostic standardization. BMC Medicine. https://doi.org/10.1186/s12916-026-05161-8

Image Credits: AI Generated

DOI: 10.1186/s12916-026-05161-8

Keywords: ME/CFS, chronic fatigue syndrome, post-exertional malaise, long COVID, post-acute infection syndromes, diagnostic criteria, consensus framework, autonomic dysfunction, cardiopulmonary exercise testing, standardized assessment

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Ophelia Keating. (September 7, 2026). International experts publish consensus framework to standardize ME/CFS diagnosis. Scienmag. https://scienmag.com/international-experts-publish-consensus-framework-to-standardize-me-cfs-diagnosis/

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