A definition for “long COVID” by the National Academies of Sciences, Engineering, and Medicine (NASEM) Committee on Examining the Working Definition for Long COVID was published in June 2024.
Under this long COVID definition, and where a person also meets ME/CFS diagnostic criteria – although the exact criteria to be used are not specified, ME/CFS can be either a pre-existing “condition” (i.e. a person may have ME/CFS, and then go on to receive a diagnosis of long COVID), or a “new condition” which develops as a result of long COVID.
More recently, a summary of this definition – and the process used to develop it, has been provided in a paper published in the New England Journal of Medicine. Following on from a previous article by ME Research UK, which introduces the NASEM definition for long COVID, the following will discuss the development of the definition in more detail including how ME/CFS fits in, and reflect on potential implications for research and clinical practice.
Why was the NASEM definition for long COVID developed?
- Although other definitions long COVID exist, such as the 2020 NICE definition in the UK and 2022 World Health Organisation definition for Adults, it was stated that ‘none have gained wide acceptance and support from patients, clinicians, researchers, and government agencies’.
- In recognition of the “shortcomings of the existing definitions”, NASEM was tasked with “developing an improved definition for long COVID that would take into account the needs of patients as well as the views and understanding of a range of experts”.
How was the definition developed?
- The authors of the paper state that “as the committee found no standardized guidelines for developing a disease definition, apart from a few cautions about things to avoid, such as stigmatizing a group or place”, the committee determined 5 key criteria that would guide the development of a long COVID definition:
- Accuracy and precision.
- Feasibility in application.
- Acceptability to affected parties.
- Accessibility and understandability.
- Balancing benefits and harms – including the potential effect on health equity and unintended consequences.
- The committee used two key methods to develop the definition:
- Consultation with people who have lived experience of long COVID – using focus groups, a questionnaire, a public comment portal, and several public meetings. (The detailed findings from this process have been published in a publicly available report.)
- Scrutinisation of existing definitions for long COVID, and analysis of published studies – including reviews, relating to the condition.
What is the NASEM definition of long COVID?
The full version of the definition is available in the recently published report, and a more detailed description has also been provided by ME Research UK, but in summary includes:
A core description of long COVID.
“Long COVID (LC) is an infection-associated chronic condition (IACC) that occurs after SARS-CoV-2 infection and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems.”
Long COVID can present in multiple ways – any organ system can be involved, and patients can present with single or multiple symptoms, and single or multiple diagnosable conditions.
A list of common symptoms.
These include post-exertional malaise (PEM), persistent fatigue, difficulty concentrating, sleep disturbance, problems with taste, problems with smell, and recurring headaches.
A summary of diagnosable conditions
These can be new, or a worsening of, pre-existing conditions; conditions referred to in the report include ME/CFS, cardiovascular disease, Postural Orthostatic Tachycardia syndrome (among other forms of dysautonomia), Lupus, and Rheumatoid Arthritis.
A description of important features of long COVID.
This section states that that long COVID can:
- Affect children and adults regardless of several factors including health, disability, and socioeconomic status.
- Resolve over a period of months, or persist for months or years. Impair patient’s ability to work, attend school, and care for themselves.
- Is not a diagnosis of exclusion – This is in contrast with the 2020 NICE definition, which specifies that Long COVID symptoms must not be “explained by an alternative diagnosis.”
Notably, a diagnosis of long COVID can be given when “symptoms or conditions are intermittently or continuously present for at least 3 months” following infection with SARS-CoV-2 which may be either “recognized, or unrecognized” meaning that a positive COVID test is not required for a diagnosis of long COVID under the 2024 NASEM definition.
The authors of the criteria state that “The committee intends its definition to be applied to many purposes.” They go on to explain that these purposes include both clinical practice and research.
Comment from ME Research UK
While the new summary paper highlights that the NASEM long COVID definition has been developed using a rigorous process – including those with lived experience of the condition, there are several potential limitations relating to ME/CFS that must be taken into consideration.
Due to issues relating to COVID-19 testing sensitivity, the 2024 NASEM long COVID definition does not require a positive COVID-19 test to qualify for a long COVID diagnosis. It is stated that where a patient does not have a positive test, clinical judgment must be used to decide whether the patient’s clinical picture fits a Long COVID diagnosis.
However, the new definition does not explain how medical professionals are to distinguish between ME/CFS and long COVID upon presentation of a person experiencing symptoms common to both (PEM, persistent fatigue, difficulty concentrating, and sleep disturbances) following either an acute infection which may or may not have been COVID-19, or onset of these symptoms following an asymptomatic infection – or another cause.
The only differentiation appears to be the duration of symptoms; 3 months for a diagnosis of long COVID, and 6 months for ME/CFS (under the IoM/NAM diagnostic criteria). This may mean that those with ME/CFS could be given a long COVID diagnosis at 3 months of ongoing symptoms when the infection that triggered the illness was another virus e.g. influenza, and not COVID-19.
An additional area that may further complicate the diagnostic procedure when using the new NASEM definition for long COVID is that the definition states:
“presence of symptoms like … post-exertional malaise, which are not common features of other medical conditions, would point towards Long COVID.”
PEM is known to be a core symptom of ME/CFS – and one recognised as essential for a diagnosis of ME/CFS to be made under the 2015 Institute of Medicine (now the National Academies of Medicine) definition. Failing to acknowledge that PEM is also a key feature of ME/CFS may further complicate the diagnostic procedure for both health professionals and researchers, especially where those applying the definition are not familiar with ME/CFS.
Additionally, the lack of explanation that PEM is also a key feature of ME/CFS within the NASEM long COVID definition may contribute to the stigma associated with ME/CFS.
ME/CFS is a disease that differs from person to person in relation to several factors, for example; disease severity, disease progression, symptoms, co-morbidities, and disease triggers. Therefore, there may also be differences between those who developed ME/CFS before the COVID-19 pandemic, and those whose symptoms have developed following a COVID-19 infection – i.e. ME/CFS as a “Diagnosable condition” within long COVID. Whether or not ME/CFS symptoms developed as part of long COVID – i.e. after a COVID-19 infection, must be taken into consideration by researchers when investigating both ME/CFS, and long COVID. It may also be an important consideration for clinicians to make when making decisions in practice relating to care and treatment plans.
The limitations summarised above present challenges for both health professionals and researchers. In clinical practice, the process of ensuring that people receive a correct diagnosis and appropriate treatment may be complicated, and for researchers investigating both ME/CFS, and long COVID, the challenge of accurate case definition (ensuring that those with a certain disease – or characteristic, of interest) becomes more complex. Although the NASEM long COVID definition does provide some advice to clinicians – that clinical judgment is required, and to researchers
More research is needed into ME/CFS, and long COVID, including identifying ways clinicians – and researchers, can distinguish between ME/CFS and long COVID in the absence of validated biomarkers for diagnosis. It is also key that researchers take into account factors that can lead to differences between people with ME/CFS, which may also now include whether or not someone has a diagnosis of long COVID in addition to their ME/CFS – and whether ME/CFS symptoms started before, or after the onset of long COVID.
