Illness presentation and quality of life in myalgic encephalomyelitis/chronic fatigue syndrome and post COVID-19 condition: a pilot Australian cross-sectional study

Purpose Post COVID-19 Condition (PCC), being persistent COVID-19 symptoms, is reminiscent of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)—a chronic multi-systemic illness characterised by neurocognitive, autonomic, endocrinological and immunological disturbances. This novel cross-sectional investigation aims to: (1) compare symptoms among people with ME/CFS (pwME/CFS) and people with PCC (pwPCC) to inform developing PCC diagnostic criteria; and (2) compare health outcomes between patients and people without acute or chronic illness (controls) to highlight the illness burdens of ME/CFS and PCC. Methods Sociodemographic and health outcome data were collected from n = 61 pwME/CFS, n = 31 pwPCC and n = 54 controls via validated, self-administered questionnaires, including the 36-Item Short-Form Health Survey version 2 (SF-36v2) and World Health Organization Disability Assessment Schedule version 2.0 (WHODAS 2.0). PwME/CFS and pwPCC also provided self-reported severity and frequency of symptoms derived from the Canadian and International Consensus Criteria for ME/CFS and the World Health Organization case definition for PCC. Results Both illness cohorts similarly experienced key ME/CFS symptoms. Few differences in symptoms were observed, with memory disturbances, muscle weakness, lymphadenopathy and nausea more prevalent, light-headedness more severe, unrefreshed sleep more frequent, and heart palpitations less frequent among pwME/CFS (all p < 0.05). The ME/CFS and PCC participants’ SF-36v2 or WHODAS 2.0 scores were comparable (all p > 0.05); however, both cohorts returned significantly lower scores in all SF-36v2 and WHODAS 2.0 domains when compared with controls (all p < 0.001). Conclusion This Australian-first investigation demonstrates the congruent and debilitating nature of ME/CFS and PCC, thereby emphasising the need for multidisciplinary care to maximise patient health outcomes. Supplementary Information The online version contains supplementary material available at 10.1007/s11136-024-03710-3.

A diagnosis of ME/CFS typically requires patients to fulfil the Canadian Consensus Criteria (CCC) [11] or International Consensus Criteria (ICC) [12], in which ME/ CFS is considered when a specified number of symptoms from each symptom category are present.Numerous case definitions have been established to describe the clinical syndrome of persistent COVID-19 symptoms following the resolution of acute viral infection [36,37], typically requiring (1) previous SARS-CoV-2 infection, which may be laboratory confirmed or clinically suspected; and (2) at least one symptom that is persistent or new in onset following acute COVID-19 illness [1,35,37].However, there exists discrepancy between PCC case definitions in the minimum illness duration required, which ranges from 4 weeks to 3 months post-infection [36,37].
Symptoms must persist for at least 12 weeks after acute illness to fulfil the case definition developed by the World Health Organization (WHO) for 'Post COVID-19 Condition' [1], the National Institutes for Health and Excellence for 'Post-COVID-19 Syndrome' [35], and the European Society for Microbiology and Infectious Disease for 'Long COVID' [37].The WHO case definition [1] additionally requires symptoms to impact one's daily life.However, due to their relatively broad and non-specific nature, established case definitions for PCC likely capture a collection of post-COVID-19 sequelae [33,38] and are unable to distinguish between COVID-19 survivors with tissue-specific damage and those with multi-systemic post-viral illness akin to ME/CFS [3,15,33,39].
Such resemblance in the clinical presentation, as well as the aetiology and physiological findings, of these two illnesses portend the potential role of ME/CFS in the illness progression of PCC [9,10,15].This has important implications for refining PCC diagnostic criteria, in which guidelines informed by existing approaches to ME/CFS diagnosis may aid in identifying patients at risk of long-term illness and thereby facilitate early interventions to maximise patient health outcomes [9,16,26].The present, exploratory investigation therefore aims to provide further insight into the illness presentation of PCC through detailed comparisons of symptom presentation among pwME/CFS and pwPCC.
In the existing literature, stringent case criteria to ascertain cohorts of pwME/CFS and pwPCC are not consistently employed to reduce potential confounding due to other medical conditions [19,30,[44][45][46][47]. Additionally, published illness presentation data largely pertains to prevalence and symptoms are often compared in clusters rather than individually [30,44,46,47].This is the first study to directly compare symptom prevalence, severity and frequency among patients that fulfil stringent case criteria, including pwME/ CFS meeting the CCC [11] or ICC [12] and pwPCC meeting the WHO case definition [1].Such data is necessary for identifying similarities between these two illnesses, as well as understanding nuanced differences, to further develop PCC diagnostic criteria and tailored care protocols.
Considering these two illness cohorts in parallel also has important implications for care and policy due to their congruency in patients' illness experiences [3,16,48].While pharmacological interventions to manage ME/CFS and PCC symptoms have been proposed, there does not currently exist a universal curative therapy or pharmacological treatment capable of counteracting the pathophysiology of ME/CFS or PCC [3,8,13,35].Consequently, both illnesses require integrated, multidisciplinary management approaches to mitigate symptoms and impacts on life [8,13,35,48].
Significantly compromised patient-reported health outcomes, including poor quality of life (QoL) and reduced functional capacity, have been reported among both pwME/ CFS and pwPCC when compared with people without acute or chronic illness [49][50][51][52][53][54][55].Research has suggested that impairments in health outcomes may persist among people reporting PCC recovery [56]; however, there is a paucity of data among recovered PCC cohorts and the findings in the existing literature are inconclusive [57].All domains of QoL and functional capacity are affected by ME/CFS and PCC and, importantly, both illnesses considerably disrupt patients' ability to perform typical activities of daily and working life [51][52][53][58][59][60].Such limitations in functioning range from a reduced capacity to maintain employment to an inability to independently perform self-care activities [8,31,[61][62][63].Hence, access to assistance from disability and social support services is paramount for pwME/CFS and pwPCC [61,[63][64][65][66].However, pwME/CFS and pwPCC commonly face challenges in accessing necessary care and support both internationally and in the Australian context [61,63,64,[67][68][69].
In Australia, pwME/CFS and pwPCC are often deemed ineligible for necessary services such as income support or care subsidies [61,64,70].To elucidate the impacts of these illnesses on patients' lives and thereby provide evidence for improved care and support accessibility, this Australian-first investigation aims to compare the QoL and functional capacity of pwME/CFS and pwPCC with people without acute or chronic illness (controls).Poorer QoL and functional capacity scores across all domains were anticipated among the pwME/CFS and pwPCC when compared with controls.Hence, this study serves to inform changes to Australian healthcare policy that facilitate the provision of adequate and appropriate care and support to foster the best possible health outcomes for Australians living with these chronic multi-systemic illnesses.

Study setting
This pilot cross-sectional study was conducted at the National Centre for Neuroimmunology and Emerging Diseases (NCNED) on the Gold Coast, Queensland, Australia from 1st March 2021 and 31st August 2022.The sample population for this study was obtained from the NCNED's participant database, which includes pwME/CFS, pwPCC and controls who have responded to study advertisements distributed via the research centre's newsletters, social media posts and collaborating physicians.Upon enrolment, all participants in the NCNED's database completed the centre's Research Registry Questionnaire-a self-administered survey, which has been described previously [71].LimeSurvey (Carsten, Schmitz, Hamburg, Germany) [72] [73] and the World Medical Association Declaration of Helsinki [74].The present study also adheres to the Strengthening the Reporting of Observational Studies in Epidemiology Statement guidelines (S1 Table , Online Resource 1) [75].

Study participants
Informed consent was electronically obtained from all study participants prior to their participation.Participants' anamnesis (including any previous and current or active illnesses, injuries or surgeries) was collected to confirm their illness status (either a person with ME/CFS, a person with PCC or control), as well as to identify any comorbid manifestations or exclusionary diagnoses.Controls were defined in this study as those who did not report a formal diagnosis of any chronic health condition and had no evidence of underlying illness.PwPCC were required to fulfil the WHO definition [1] for PCC.Additional criteria for pwME/CFS included: (1) currently fulfilling or having a history of fulfilling at least one of the CCC [11] or ICC [12] for ME/CFS, (2) having had received a formal diagnosis of ME/CFS from a physician, and (3) not reporting a history of acute COVID-19 illness prior to ME/CFS onset.To ensure that the findings of the present study are appropriately attributed to ME/CFS and PCC and are not confounded by comorbid or pre-existing medical conditions, reported history of other formally diagnosed disease pathologies (such as genetic, metabolic, immunological (including autoimmune disease), neurological, cardiovascular, or respiratory disease), malignancy within the last 5 years, and formally diagnosed mental illness, chronic multi-systemic illness, or other post-viral illness were considered exclusionary.Respondents with concurrent or subsequent diagnoses of anxiety, depression, or overlapping chronic pain conditions captured within ME/ CFS diagnostic criteria (such as fibromyalgia and irritable bowel syndrome) were not excluded [8,11,12].

Sociodemographic characteristics
The following sociodemographic information was requested from all study participants via the Research Registry Questionnaire: age, sex assigned at birth, body mass index (BMI), Australian state of residence, highest level of education completed, employment status and (for participants who were not employed at the time of completing the questionnaire) whether illness or disability was responsible for unemployment.

Illness characteristics and symptom presentation
All pwME/CFS and pwPCC completed the Research Registry Questionnaire and provided their illness duration, as well as symptom presentation (including symptom presence, severity and frequency) within the month prior to completing the questionnaire.Illness duration was calculated from the month and year in which participants reported first experiencing symptoms of their chronic multi-systemic illness.The symptoms assessed were derived from the CCC [11] and ICC [12] and align with the manifestations within the WHO case definition [1] for PCC.Hence, the questionnaire captured participants' self-perceived experiences of postexertional malaise, as well as symptoms from six major symptom categories, including: (1) Cognitive disturbances (impaired concentration and short-term memory loss); (2) Pain (headache, myalgia, arthralgia (without redness or swelling) and abdominal pain); (3) Sleep (sleep disturbances, such as insomnia, prolonged sleep (including naps), frequent awakenings, vivid dreams or nightmares and unrefreshed sleep); (4) Neurosensory, perceptual and motor disturbances (photophobia, sensitivity to noise or vibration, sensitivity to odour or taste and muscle weakness); (5) Immune, gastrointestinal and urinary disturbances (lymphadenopathy, laryngitis, nausea, bloating, altered bowel habits, such as diarrhoea and constipation, and urinary frequency or urinary urgency); and (6) Other autonomic manifestations (heart palpitations, light-headedness or dizziness, dyspnoea, sweating episodes, recurrent feelings of feverishness and cold extremities).
Symptom presence was defined as both: (1) having been experienced at least 'a little of the time' and at least at a 'very mild' level of severity; and (2) having been reported by the participant as being attributable to their chronic multisystemic illness.PwME/CFS and pwPCC were subsequently categorised based on the most stringent ME/CFS case definition met according to their symptom presentation.Symptom severity and frequency were quantified on the five-point Likert scales employed in the 2005 Centers for Disease Control and Prevention's Symptom Inventory Questionnaire for ME/ CFS [76].Symptom severity was measured as: (1) very mild, (2) mild, (3) moderate, (4) severe or (5) very severe, and symptom frequency as: (1) a little of the time, (2) some of the time, (3) a good bit of the time, (4) most of the time or (5) all the time.

Patient-reported outcome measures
Five validated patient-reported outcome measures (PROMs) were employed in this study to capture the participants' QoL and functional capacity.All pwME/CFS, pwPCC and controls completed the 36-Item Short-Form Health Survey version 2 (SF-36v2) [77] and the World Health Organization Disability Assessment Schedule version 2.0 (WHODAS 2.0) [78].

SF-36v2
The SF-36v2 [77] assesses QoL across eight domains, including Physical Functioning, Role Limitations due to Physical Health Problems (also known as Role Physical), Bodily Pain, General Health Perceptions, Vitality, Social Functioning, Role Limitations due to Personal or Emotional Problems (also known as Role Emotional), and General Mental Health.Domain scores were calculated according to the scoring instructions in the version 2 update [77].

Secondary PROMs
Participants were also invited to complete a second selfadministered questionnaire comprising three additional validated PROMs for health and wellbeing, including the Hospital Anxiety and Depression Scale (HADS) [79], the Modified Fatigue Impact Scale (MFIS) [80], and Dr Bell's Chronic Fatigue and Immune Dysfunction Syndrome (CFIDS) Disability Scale [81].In addition to the Research Registry Questionnaire, the secondary PROMs questionnaire was completed by n = 29 pwME/CFS, n = 14 pwPCC and n = 8 controls.

Statistical methods
Data analysis was performed with Statistical Package for the Social Sciences version 29 (IBM Corp, Armonk, New York) [82].The statistical tests performed and reporting of results align with the Statistical Analysis and Methods in the Published Literature guidelines [83].For continuous data, homogeneity of variances was assessed with Levene's test and normality was investigated with Shapiro-Wilk (if n < 50) and Kolmogorov-Smirnov (if n ≥ 50) tests.The α-level for all statistical analyses was 0.05 and the results of any post-hoc analyses presented are p < 0.05 after correction for multiple comparisons.All p-values are provided to two significant figures except where p < 0.001.The number and percentage of participants with missing data are reported for each variable where applicable.
Categorical variables were compared between the study cohorts with Chi-square, Fisher-Freeman-Halton and Fisher's exact tests.Post-hoc analyses for categorical variables were performed using pairwise comparisons and the Benjamini-Hochberg correction.Non-normally distributed continuous variables were compared between the study cohorts using Mann-Whitney U and Kruskal-Wallis H tests, with Dunn-Bonferroni post-hoc analyses and the Benjamini-Hochberg correction employed where applicable.To compare the non-parametric QoL scores of the cohorts while controlling for age and sex (as well as illness duration, where applicable), partial rank correlations were generated for the three possible pairings of the study cohorts and were subsequently adjusted for multiple comparisons with the Benjamini-Hochberg correction.For all relevant QoL comparisons, confounding variables were investigated using linear regression models and, where applicable, were analysed as covariates to confirm the robustness of the results.Reliability statistics were generated for all subscales of the QoL PROMs (except for Dr Bell's CFIDS Disability Scale, as this PROM is a single-item measure).For each subscale, internal consistency was evaluated with McDonald's ω. Sufficient internal consistency was defined as ω ≥ 0.7 [84].

Results
The NCNED's participant database (n = 1200) was screened for eligible study participants.Of the database participants, 250 people were deemed eligible.Data were available for n = 146 participants who had provided informed consent for prospective studies, including n = 61 pwME/CFS, n = 31 pwPCC and n = 54 controls.

Illness characteristics
The illness characteristics of the pwME/CFS and pwPCC are summarised in Table 2. Most pwME/CFS fulfilled the ICC [12] (65.6%, n = 40), while 32.8% (n = 20) fulfilled the CCC [11].One participant (1.6%) fulfilling the Fukuda criteria [85]-an earlier case definition for ME/CFS broader than the CCC [11] and ICC [12]-at the time of completing the questionnaire was included in the present study due to a history of meeting more stringent criteria and fluctuating symptoms.All pwPCC (100.0%,n = 31) met the WHO case definition [1] for PCC, with 58.1% (n = 18) also fulfilling at least one of the three diagnostic criteria for ME/CFS.

Symptom presentation
Table 3 presents the results of symptom prevalence, severity and frequency comparisons between the two illness cohorts.
Complete symptom presentation data are summarised in S2 to S3 Tables, Online Resource 1. Severity and frequency distributions for symptoms that differed significantly between the two cohorts are presented in Fig. 1.

Quality of life and functional capacity
Summary statistics for all QoL PROMs are provided in Table 4.For all PROMs, poorer QoL scores were observed among pwME/CFS and pwPCC in every domain (except HADS Anxiety) when compared with controls (p < 0.001, uncorrected).PwME/CFS and pwPCC did not differ significantly in any domain of the QoL PROMs.
Complete reliability statistics for each subscale of the QoL PROMs are provided in S4

WHODAS 2.0
Life Activities 1 was associated with the greatest illness impact of all the WHODAS 2.0 domains among the ME/CFS (M = 80.00, Q1-3 = 50.00-100.00,95% CI = 60.00-90.00)and PCC participants (M = 70.00,Q1-3 = 40.00-90.00,95% CI = 40.00-90.00).Self-Care was the WHODAS 2.0 domain least impacted by the participants' illness in both the ME/CFS (M = 30.00,Q1-3 = 10.00-50.00,95% CI = 20.00-40.00)and PCC (M = 0.00, Q1-3 = 0.00-40.00,95% CI = 0.00-30.00)groups.Self-reported and believed by participant to be attributable to either ME/CFS or PCC (depending on illness status).This does not include participants with missing data, nor does this include participants who stated that they, within the month prior to completing the questionnaire, did not experience the symptom in question, were unsure if they had experienced the symptom in question, had experienced the symptom in question but were unsure if the symptom was attributable to their chronic multi-systemic illness or had experienced the symptom in question but believed that the symptom was not attributable to their chronic multi-systemic illness (additional data, including the participants with missing data, is provided in S2 and S3 Tables, Online Resource 1).b Among those who reported experiencing the symptom in question within the month prior to completing the questionnaire and believed the symptom to be attributable to their chronic multi-systemic illness.

Discussion
The present study shares novel, detailed comparisons of illness presentation among pwME/CFS and pwPCC fulfilling stringent diagnostic criteria and investigates the impacts of these illnesses on patients' QoL and functional capacity when compared with controls.This vital investigation further characterises the illness presentation of PCC, identifying remarkable similarities of this emerging illness with ME/CFS.These findings provide insight into the clinical case definition of PCC, as well as the potential use of existing ME/CFS management approaches among pwPCC.Additionally, this publication documents the profound and widespread illness burden experienced by pwME/CFS and pwPCC in Australia, thereby necessitating health policy reforms that facilitate improved accessibility of necessary care and support services for Australians living with these illnesses.The present study observed marginal differences in illness presentation between pwPCC and pwME/CFS, with notable similarities between the two cohorts in key symptoms typically experienced by pwME/CFS, such as post-exertional malaise, neurocognitive dysfunction and sleep disturbances.All pwME/CFS and pwPCC providing valid symptom data experienced post-exertional malaise in the current study.[44,87], the appearance of the hallmark symptom of ME/CFS among this novel illness cohort suggests that post-exertional malaise is a noteworthy component of the PCC illness presentation and should be considered in diagnostic criteria and care provision.
Like the present investigation, international studies have similarly reported a comparable prevalence of key ME/ CFS symptoms among people with persistent COVID-19 symptoms [19,[44][45][46][47][86][87][88].Among the cardinal ME/CFS symptoms, only memory loss was significantly more prevalent (p = 0.039) and unrefreshed sleep significantly more frequent (p = 0.011) among pwME/CFS than pwPCC in the present study.However, this may be explained by 51.6% of PCC participants not fulfilling stringent ME/CFS case criteria, as Kedor et al. observed comparable prevalence and severity of memory problems and sleep disturbances among pwME/CFS and pwPCC meeting the CCC [47].
The few remaining significant differences in symptom presentation between the cohorts included a higher   [11] for ME/CFS) and pwME/ CFS [47].Most symptoms were comparable in presentation in a study by Azcue et al. among people meeting the WHO case definition [1] for PCC and pwME/CFS; however, differences were observed in the severity and frequency of pain, thermostatic, neurosensory and gastrointestinal symptoms, as well as weight changes and unrefreshed sleep [45].Unlike the present investigation, Jason et al. reported significant differences in the severity of most symptoms, except neurocognitive disturbances, among people with self-reported persistent COVID-19 symptoms (without a minimum illness duration threshold) and pwME/CFS [19].Hence, the overlap of key ME/CFS symptoms, in addition to the disparity in the literature regarding the presentation of accessory symptoms, foregrounds the importance of developing PCC diagnostic criteria capable of delineating illness subtypes, including those with ME/CFS-like illness, with sufficient specificity.
In the present study, 58  [88,89].However, this may be due to participants in these studies having an illness duration of less than 6 months (a minimum illness duration threshold required by many ME/ CFS case definitions [90]), in which Aly et al. observed that 53% of their study population would have met ME/CFS criteria had illness duration requirements been met [91].Hence, fulfilment of ME/CFS criteria following acute COVID-19 illness may be an indicator of illness trajectory and a means of identifying pwPCC at risk of long-term illness.
While observational studies have reported recovery within 12 months in 40 to 50% of people with persistent COVID-19 symptoms [92,93], the long-term health outcomes of PCC are not yet known [3].Nevertheless, the findings of the present study underscore the risk of developing permanent chronic illness and disability following acute COVID-19 illness and foreground the potential role of ME/ CFS in the illness progression and diagnosis of PCC.This also has important ramifications for estimating the future healthcare burdens of post-COVID-19 sequelae (as over 90% of people with ME/CFS experience life-long illness [18,94]) and emphasises the importance of reducing SARS-CoV-2 transmission [95,96].
The analogous QoL and functional capacity observed among pwME/CFS and pwPCC (in both the present and existing publications [27,47]) also highlights the profound and widespread impact of this novel illness and validates the illness experiences of pwPCC, who continue to face stigma [63,97,98].This publication echoes existing findings that ME/CFS and PCC have a noteworthy impact on one's ability to perform daily activities due to physical functional limitations [51][52][53][58][59][60], with the SF-36v2 Role Physical, WHODAS 2.0 Life Activities 1, WHODAS 2.0 Participation and MFIS Physical scores among the poorest of their corresponding PROMs.SF-36v2 Vitality scores were also notably poorer among pwME/CFS and pwPCC when compared with controls, indicating considerable impairments in energy interfering with life activities.
These findings exemplify the physically disabling nature of ME/CFS and PCC, which must be considered in the provision of care for people with these illnesses.The congruent impairments in QoL and functional capacity are also of note due to the significantly shorter illness duration of PCC when compared with ME/CFS.Importantly, the impacts on daily activities observed in this study emphasise the need for integrated approaches across the healthcare, disability and social support sectors for pwME/CFS and pwPCC in Australia [35,61,64,66].Access of disability and social support services has long been an arduous process for Australians with ME/CFS and, more recently, for those with PCC, with neither illness currently recognised as a disability in Australian health policy [61,64].These findings, combined with the high prevalence of post-exertional malaise, also have implications for clinical practice, reinforcing the importance of pacing strategies and engagement of allied health professionals, such as occupational therapists, in the management of ME/CFS, as well as PCC [3,8,13,31,32].
Mental health outcomes, including the SF-36v2 Role Emotional, SF-36v2 Mental Health and HADS Depression subscales, were significantly impacted among pwME/CFS and pwPCC when compared with controls in the present study.However, it is worth noting that mental health outcomes were the least affected of the QoL PROM domains and that these impacts are likely secondary to living with chronic illness and are not the primary cause of either ME/ CFS or PCC [8].In the present study, the HADS Anxiety subscale was the only QoL PROM domain that was not significantly different among the pwME/CFS and pwPCC when compared with controls.There was also no significant difference in the distribution of potential or probable anxiety or depression cases (determined via the HADS) among the three study cohorts.However, as the HADS was a component of the secondary PROM questionnaire, which was completed by a subset of the total study population, the of significance in the HADS subscales may be due to the smaller sample size.

Strengths and limitations
It should be noted that the present cross-sectional study captured data at a single point in time.Detailed longitudinal data using a larger sample size is paramount to understand the relationship between PCC symptoms at onset, including ME/CFS-like illness presentation, and prognosis.Future longitudinal research should also correlate the trajectory of symptoms with the pathologies that have been identified among the two illnesses.Additionally, comparisons between pwPCC and pwME/CFS who have a comparable illness duration are warranted to determine whether the differences in symptom presentation are illness-or time-dependent [19].
The potential for volunteer bias in the present study must be acknowledged, as participants provided questionnaire data when participating in other projects at the NCNED research centre [27, 28, Some pwPCC providing symptom and health outcome data earlier in their illness progression prospectively fulfilled the WHO case definition [1] and therefore were still deemed eligible for inclusion in the present study.This current investigation also utilises self-reported data and, as the survey responses are subjective, participants may not assess themselves similarly.Employment data should be interpreted with caution, as most pwPCC who reported being in full-time employment stated that they were on sick leave or organised reduced working hours.Finally, the study cohorts may underrepresent the illness experiences of people from marginalised populations.Future inclusive research is required to inform tailored approaches to care and support for people belonging to marginalised populations who live with ME/CFS or PCC in Australia.
Importantly, this investigation serves as a pilot study providing novel patient experience data to inform Australian healthcare policy.Validated diagnostic criteria were employed to ascertain the study cohorts, including the CCC [11] and ICC [12] for ME/CFS and the WHO case definition [1] for PCC.These diagnostic criteria are the most stringent criteria available and, for this reason, were employed to ensure people with other chronic illnesses were not selected into the study sample [13,102].The use of validated measures of symptom presentation and QoL also mitigated the potential for information bias.

Conclusions
The manifestations of ME/CFS and PCC are remarkably similar, with marginal differences in symptoms and QoL.Key ME/CFS symptoms (including post-exertional malaise, unrefreshed sleep and neurocognitive impairments) were comparable in presentation between the two illness cohorts.Both ME/CFS and PCC are associated with significant disruptions to life and have an immense and widespread impact on QoL and functioning.This research thereby provides important insight into the presentation and potential prognosis of PCC, serving to guide further development of diagnostic case definitions and care pathways.Additionally, this research foregrounds the illness burdens of ME/CFS and PCC and, consequently, the necessity of accessible multidisciplinary healthcare, disability and social support services for people living with these chronic multi-systemic illnesses.Such patient experiences must be considered in Australian healthcare policy to optimise health outcomes for pwME/CFS and pwPCC in Australia.
c Likert scale values: (1) Very mild; (2) Mild; (3) Moderate; (4) Severe and (5) Very severe.d Likert scale values: (1) A little of the time; (2) Some of the time; (3) A good bit of the time; (4) Most of the time; (5) All the time.e Includes manifestations such as insomnia, prolonged sleep (including naps), frequent awakenings and vivid dreams or nightmares.f Includes manifestations such as diarrhoea and constipation

Fig. 1
Fig. 1 Severity and frequency for symptoms returning significance between the two illness cohorts.Figure generated with GraphPad.PwME/CFS people with myalgic encephalomyelitis/chronic fatigue syndrome, PwPCC People with Post COVID-19 Condition.Symptom 95% CI 95% confidence interval, C consensus, CFIDS chronic fatigue and immune dysfunction syndrome, HADS hospital anxiety and depression scale, M median, MFIS modified fatigue impact scale, PwME/CFS people with myalgic encephalomyelitis/chronic fatigue syndrome, PwPCC people with post COVID-19 condition, Q1-3 quartile 1 to 3, SF-36v2 36-item short-form health survey (version 2), WHODAS 2.0 World Health Organization disability assessment schedule (version 2.0) Uncorrected p-values are reported for each partial correlation model.Bolded uncorrected p-values indicate significance (p < 0.05) after correction for multiple comparisons.Any changes in significance arising from robustness checks are reported a Data available for n = 61 pwME/CFS, n = 31 pwPCC and n = 53 controls.Data missing for n = 1 control.All QoL PROM subscales were nonparametric and analysed with partial rank correlations controlling for age and sex (as well as illness duration for comparisons between the pwME/CFS and pwPCC).b QoL PROM data was not provided for n = 1 control.c Each domain has a minimum score of 0 and a maximum score of 100.d Values provided for n = 29 pwME/CFS, n = 14 pwPCC and n = 8 controls.e Each domain has a minimum score of 0 and a maximum score of 21. f This domain has a minimum score of 0 and a maximum score of 36.g This domain has a minimum score of 0 and a maximum score of 40.h This domain has a minimum score of 0 and a maximum score of 8. i Values presented are reflective of percentage total functioning with a minimum score of 0.0% and a maximum score of 100.0%

Table 2
Illness characteristics of and diagnostic criteria met by all study participants 95% CI 95% confidence interval, CCC Canadian Consensus Criteria, HADS hospital anxiety and depression scale, ICC International Consensus Criteria, M median, NA not applicable, PwME/CFS people with myalgic encephalomyelitis/chronic fatigue syndrome, PwPCC people with post COVID-19 condition, Q1-3 quartile 1 to 3, WHO World Health Organization Bolded p-values indicate significance a Mann-Whitney U statistic.b Percentage of those fulfilling at least the Fukuda case definition.c Fisher-Freeman-Halton exact test statistic.d Values provided for n = 29 ME/CFS participants, n = 14 PCC participants and n = 8 controls

Table 3
Summary of symptom presentation comparisons between the ME/CFS and PCC participants C consensus, M median, NA not applicable, PwME/CFS people with myalgic encephalomyelitis/chronic fatigue syndrome, PwPCC people with post COVID-19 condition Bolded p-values indicate significance (p < 0.05) a

Table 4
Quality of life among all study participants Vernon et al. and Twomey et al. reported a similar postexertional malaise prevalence of 99 and 94.8%, respectively, among people experiencing ongoing COVID-19 symptoms 86].While a lower prevalence of post-exertional malaise among people with post-COVID-19 sequelae was observed by Bonilla et al. (82.8%) and Retornaz et al. (78%)

Table 4 (
.1% of pwPCC fulfilled ME/CFS criteria.The prevalence of ME/CFS among people with persistent COVID-19 symptoms was reported by Kedor et al. and Bonilla et al. as 45.2 and 43%, respectively [47, 87].Other studies have observed considerably lower proportions of people with ongoing COVID-19 symptoms fulfilling ME/ CFS criteria, with the prevalence of ME/CFS reported as 16.8% by Tokumasu et al. and 8.1% by AlMuhaissen et al.