Estimating ME/CFS prevalence in individuals with long COVID

Key points

  • Long COVID and ME/CFS have overlapping symptoms, yet many studies overlook the proportion of individuals with long COVID who meet ME/CFS criteria.
  • Improving on previous research, Dr Leonard Jason and Joseph Dorri’s study reveals that 58% of their long COVID participants met ME/CFS criteria. Nevertheless, the authors acknowledged the study’s limitations and emphasise the need for long-term follow-up.
  • To improve future long COVID studies, symptom questionnaires such as DSQ-PEM could aid in determining the proportion of participants meeting ME/CFS criteria.
  • Given the predicted rise in disease burden and economic costs linked to ME/CFS as a result of the COVID-19 pandemic, thorough investigation is imperative.


During the early phases of the COVID-19 pandemic, as the term ‘long COVID’ first emerged, Dr Anthony Komaroff raised a crucial question in an article: “Will some people who get COVID-19 subsequently develop ME/CFS?” He further stated, “After all, many people with ME/CFS say that their illness began with some kind of infection: a virus, a flu, a bad cold.”

Dr Komaroff, a senior physician with over 270 publications, explored this possibility, noting that ME/CFS often manifests after infectious episodes. His article highlights evidence that ME/CFS can follow both “apparently infectious illnesses of uncertain cause” and clearly diagnosed infectious diseases, such as those associated with the SARS and West Nile Virus epidemics. The article concludes with the statement, “It is therefore entirely plausible that some cases of ME/CFS will develop in people who get COVID-19. It is important to conduct studies that follow people with COVID-19 for several years, even after they recover, to see whether ME/CFS or other long-term complications will develop.”

Is long COVID always a separate entity from ME/CFS?

Often with the help of government funding, there have been numerous studies investigating possible underlying mechanisms and management strategies. However, researching long COVID is potentially challenging as the condition is associated with over 200 symptoms across multiple organ systems, and has no set of core symptoms required to be present for a diagnosis. Essentially, long COVID is a ‘catch-all’ term for symptoms which persist following a SARS-CoV-2 (COVID-19) infection, and it could therefore be difficult for studies to find a focus.

In a large study funded through the NIH RECOVER initiative, the researchers questioned whether, given the heterogeneity of long COVID, it represents one unified condition or a group of unique phenotypes (observable characteristics). The study identified four subgroups of long COVID based on symptom clusters, three of which included post-exertional malaise (PEM) – a cardinal feature of ME/CFS.

In reality, much of long COVID research not only draws on the experiences of individuals with ME/CFS, but also explores items which have already been noted or investigated in ME/CFS populations such as endothelial dysfunction(problems with blood vessel lining). The similarities between long COVID and ME/CFS have frequently been acknowledged, but the two conditions have largely been treated as separate entities, despite reports of many individuals with long COVID meeting the diagnostic criteria for ME/CFS.

Dr Ron Tompkins, a Massachusetts General Hospital surgeon who researches ME/CFS, emphasised that progress hinges on “doctors definitively determining that coronavirus can turn into ME/CFS, rather than making post-coronavirus syndrome a separate diagnosis”. Yet, despite increasing knowledge of potential long-term complications following a COVID-19 infection, solid estimates of the proportion of individuals with long COVID meeting ME/CFS diagnostic criteria remain scarce.

Increasing economic costs of ME/CFS following COVID-19 pandemic

Dr Arthur Mirin and colleagues stated in a 2022 article: “A significant portion of people with long COVID are likely to develop ME/CFS, contributing to a substantial increase in ME/CFS prevalence, disease burden, and economic impact. Taking into account this expected increase in ME/CFS onset following COVID-19, we estimate the resultant US ME/CFS prevalence could range between 5 and 9 million individuals.” Also, according to evidence reported to the German Bundestag’s Health Committee, it is anticipated that around 1 to 2 percent of all SARS-CoV-2 infected people (up to 20 percent of all post-COVID sufferers) will meet ME/CFS diagnostic criteria after six months.

As mentioned in ME Research UK’s response to the DHSC interim delivery plan on ME/CFS, if the minimum cost to the UK economy was £3.3 billion prior to the onset of the COVID-19 pandemic, it must be acknowledged that this will have dramatically increased as result of increased cases of ME/CFS. Therefore, any research strategies and funding allocated to biomedical research into ME/CFS must surely reflect this.

Estimates of ME/CFS prevalence among individuals with long COVID

In December 2022, Dr Leonard Jason and Joseph Dorri published a study addressing the issue of ME/CFS prevalence amongst individuals with long COVID. The researchers noted that prior studies reported varying percentages (ranging from 13% to 58.7%) of individuals with long COVID meeting ME/CFS criteria. However, there were limitations to these studies including a small sample size, “unclear methods for determining the ME/CFS case definitions”, and a lack of comprehensive measures for PEM.

Considering the limitations of previous research, Dr Jason and Dorri aimed to make improvements in the methodology in order to determine the proportion of individuals with long COVID meeting “the ME/CFS case definition”, including PEM. The study recruited 465 participants, predominantly from social media sites dedicated to COVID-19 and communities and groups related to long COVID. The participants completed three types of DePaul Symptom Questionnaire (DSQ): DSQ-COVID – a new questionnaire measuring common symptoms of COVID and long COVID; DSQ-SF – a short form (SF) questionnaire assessing ME/CFS symptoms relating to both Canadian Consensus Criteria and Fukuda criteria; and DSQ-PEM – a brief questionnaire assessing PEM.

The findings were that a substantial proportion (58%) of participants met ME/CFS criteria. The researchers acknowledged that this study had its own limitations, including a higher female/male ratio than most studies, lack of ethnic diversity and that “study subjects were recruited from online patient communities of people whose COVID-19 was diagnosed in various ways”. Additionally, they mention that it was a cross-sectional study, and long-term follow-up would be needed to determine if ME/CFS symptoms persist in the sample population.

Another team of researchers, many whom have had projects funded by ME Research UK, recently published an opinion article also pointing out weaknesses in the ability of long COVID studies to estimate the prevalence of ME/CFS amongst participants. They state, “Given the global urgency of managing and treating LC [long COVID], several studies are combining basic research on this disease and ME/CFS with the idea of accelerating knowledge of the underlying pathological mechanisms. However, similar combined approach remains to be adopted in epidemiological studies of LC. Therefore, these studies could expand their objectives to include the estimation of ME/CFS prevalence as well.”

Analysing three large systematic reviews of long COVID prevalence, the researchers found that, despite widespread awareness of the similarities between long COVID and ME/CFS, epidemiological studies of long COVID had missed the opportunity to fully assess the presence and severity of key features of ME/CFS. Most notably, the systematic reviews did not comment on the presence of PEM, despite the fact that PEM is known to be reported in individuals with long COVID. Therefore, retrospective analysis of long COVID studies is unlikely to reveal the true prevalence of ME/CFS in long COVID populations.

The researchers recommend that future epidemiological studies of long COVID, at minimal cost, can incorporate standard symptom questionnaires (DSQ or UK ME/CFS Biobank [UKMEB] diagnosis Symptoms Assessment Questionnaire) for ME/CFS diagnosis. Furthermore, they concur with the use of DSQ-PEM as a questionnaire dedicated specifically to PEM. Additionally, they recommend reporting standard items, namely the case definition used, symptom inventory, excluded medical and psychiatric conditions and co-morbidities, and self-reported functional impairment/levels of activity.


Many individuals with long COVID report symptoms that overlap with ME/CFS, but the proportion of participants with long COVID who meet ME/CFS criteria is often not mentioned in epidemiological studies. Nevertheless, there have been a few studies which provide estimates of ME/CFS prevalence in long COVID populations, although there are significant limitations in the methodology of these studies.

Given predictions of increased disease burden and economic costs, as a result of the COVID-19 pandemic, thorough investigation is imperative. A cost-effective improvement for future long COVID studies could involve integrating symptom questionnaires, including the DSQ-PEM, and allowing for measurement of the proportion of individuals meeting ME/CFS criteria.

Furthermore, as conveyed in the DHSC interim delivery plan, there needs to be better education of and awareness amongst medical practitioners about long COVID and ME/CFS to enable appropriate management advice to be given. Hence, it may be helpful if practitioners also use ME/CFS symptom questionnaires in the assessment of patients with long COVID.

Read more about the economic burden of ME/CFS

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