Symptom description Prolonged fatigue: persistent profound fatigue or lack of energy, usually (but not necessarily) accompanied by other symptoms; should be present for at least one month Chronic fatigue (CF): persistent fatigue or lack of energy, that leads to reduced activity levels lasting over 3–6 months*. This may be explained by a condition other than ME/CFS (e.g., cancer-related fatigue) or unexplained (“idiopathic chronic fatigue”). It does not require other symptoms that are typically found in ME/CFS Post-infectious fatigue or post-viral illness (PIF or PVI): new onset symptom complex including persistent profound fatigue with exercise intolerance following an infectious trigger and which is not otherwise explained by a diagnosed condition or lifestyle. It is usually accompanied by at least 2 further symptoms** from: post-exertional malaise, unrefreshing or poor sleep quality, cognitive or autonomic symptoms for at least 3 months (i.e., this is a subset, where the viral aetiology is clear, of patients with chronic fatigue). Diagnostic categories ME or ME/CFS: persistent fatigue or lack of energy that leads to reduced activity levels lasting over 3–6 months, when diagnostic criteria according to IOM or Canadian Consensus criteria (CCC) are fully met for adults, and CCC or Rowe’s criteria are fully met in children. ME/PVFS (ME/Post-viral fatigue syndrome or post-infectious fatigue syndrome, post-infectious ME/CFS): As for ME/CFS, when symptoms follow a presumed or confirmed infection (e.g., post-COVID-19 fatigue syndrome, post-mononucleosis fatigue syndrome, post-Lyme ME/CFS) (NB. This does not preclude there being triggers other than infections involved in the origins of the illness in other cases) Non-ME chronic fatigue: chronic fatigue cases that do not fulfil the diagnostic criteria for ME/CFS, lasting for at least 3–6 months, but are attributable to other underlying causes. ME/CFS of combined aetiology: when symptoms are attributed to a combination of ME/CFS and other known disease(s), e.g., ME/CFS and diabetes type 2 (NB. This is not in itself a diagnosis, which requires identification of the disease(s) to which the condition is attributable).

Examples of stratification categories: Age-group (e.g., children, adolescents, adults, elderly), gender Illness onset: acute or gradual; post-infection, following other triggers, e.g., environment exposure Presence of co-morbidities, e.g., fibromyalgia, hypermobility, mild mood disorders Phase of disease (or disease duration), e.g., early, established, and complicated disease (Nacul et al., 2020) [7] Severity (based on symptoms score or measures of function); a broad categorisation of severe/non-severe is based on being virtually house-bound or able to regularly be outside home. Very severe cases are virtually bed-bound. Clinical phenotype: based on predominance of symptoms by type (e.g., based on CCC symptoms sub-groups); e.g., neuro-cognitive, immune, sleep phenotypes (NB. There are distinct clinical phenotypes in ME/CFS which can be identified from gene expression data [47,48]). One study identified seven genomically derived subtypes of ME/CFS which manifested distinct phenotypes [49,50]. Molecular phenotype: i.e., based on well-defined profiles based on results of specialised investigations, e.g., metabolic, immunological.

* CCC 2003 [2], IOM 2015 [6], and Rowe et al., 2017 [4], criteria require 6 months of symptoms; experienced clinicians should be able to diagnose adults with 3 months of symptoms. For children, CCC criteria requires 3 months [2], and Rowe et al., 2017 [4], require 3 months in post-infectious cases. ** The 2 additional symptoms criterium is not required when the fatigue symptoms can be clearly linked to the triggering infection and are not explained by other pathologies.