ME/CFS or post-COVID? That is the question

Is your patient affected by post-COVID or ME/CFS? Despite overlapping symptoms, there are differences between the indications. Which values should be collected for diagnosis?

The Neurology Blog
By Dr Annabelle Eckert

What is ME/CFS?

ME/CFS stands for myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS). ME/CFS is a neuroimmunological multisystem disease. The patients affected suffer from an extraordinary impairment of their physical and mental performance. In addition to the specific and characteristic main symptom of post-exertional malaise (PEM), patients also suffer from sleep and memory disorders, fatigue and pain. The cause of ME/CFS has not yet been determined. It is assumed that a dysfunction of the immune system and the autonomic nervous system are causally involved in the development of ME/CFS. 1-10 % of patients with COVID-19 can suffer from ME/CFS. The symptoms of ME/CFS and Long COVID can overlap in several ways.1-5

What role does post-exertional malaise (PEM) play in ME/CFS?

The term post-exertional malaise (PEM) refers to the exertion-induced worsening of symptoms in ME/CFS. This systemic exercise-induced intolerance can occur immediately after mildly strenuous physical or mental activity or only after 12 to 48 hours. PEM is a fundamental prerequisite for the diagnosis of ME/CFS. In addition to activities, emotions, light, noise, standing or sitting can also trigger PEM. This is partly due to the orthostatic intolerance that exists in ME/CFS. The greater the severity of ME/CFS, the lower the threshold for triggering factors. This is aggravated by the fact that ME/CFS can become chronic.1-5

Symptoms range from neurocognitive to digestive

Symptoms of ME/CFS include fever, lymph node swelling, pathological weakness, brain fog, difficulty finding words, fatigue, poor concentration, circulatory problems, sleep disorders, joint/muscle/headaches, gastrointestinal complaints, increased sensitivity to light, sounds and odours. Interestingly, ME/CFS patients show abnormal lactate accumulation after physical exercise. Even at rest, lactate levels are elevated. On the cycle ergometer, a rapid drop in performance at the anaerobic threshold can be observed in ME/CFS patients.1-5

Long COVID and ME/CFS

The symptoms of patients with Long COVID and ME/CFS patients can coincide in many respects. The majority of ME/CFS patients report a sudden onset of ME/CFS after an apparently infectious illness. This was accompanied by respiratory symptoms, fever, myalgia and adenopathy, among other things.

In a prospective cohort study, clinical and laboratory parameters were compared between patients with post-COVID syndrome with ME/CFS and ME/CFS patients (non-COVID-19). The research group was able to observe that the severity of the disease and the symptom burden in patients with post-COVID syndrome with ME/CFS were comparable to ME/CFS patients (non-COVID-19). Both study groups showed reduced hand strength (compared to normal values in healthy individuals). In post-COVID syndrome with non-myalgic encephalomyelitis/chronic fatigue syndrome, there was a correlation between hand strength and haemoglobin, interleukin 8 and C-reactive protein. In patients with post-COVID syndrome/myalgic encephalomyelitis/chronic fatigue syndrome, hand strength correlated with haemoglobin, NT-proBNP, bilirubin and ferritin. The research group therefore suspects that low-level inflammation and hypoperfusion could underlie the latter two clinical pictures.5

Long COVID or ME/CFS?

Distinguishing between patients with post-COVID syndrome and patients with ME/CFS is difficult even for the best clinicians. This is not least due to the striking overlap in symptoms. Several studies suggest that half of patients with post-COVID syndrome fulfil the ME/CFS criteria.5,6

Comorbidities in ME/CFS

ME/CFS is a highly underdiagnosed syndrome. This may be due in part to the lack of a reliable diagnostic biomarker and the heterogeneity of the clinical presentation. In 2023, the Mayo Clinic therefore published a kind of diagnostic and management guideline to rule out complicating comorbidities in ME/CFS. It recommended that the following values be collected:

References
  1. van Campen CLMC. et al. (2021). Numeric Rating Scales Show Prolonged Post-exertional Symptoms After Orthostatic Testing of Adults With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Med (Lausanne). 2021 Jan 27;7:602894. doi: 10.3389/fmed.2020.602894. PMID: 33585505; PMCID: PMC7874746.
  2. Lim EJ. et al. (2020). The Prospects of the Two-Day Cardiopulmonary Exercise Test (CPET) in ME/CFS Patients: A Meta-Analysis. J Clin Med. 2020 Dec 14;9(12):4040. doi: 10.3390/jcm9124040. PMID: 33327624; PMCID: PMC7765094.
  3. Franklin J.D. et al. (2019). Peak Oxygen Uptake in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: A Meta-Analysis. Int J Sports Med 2019; 40(02): 77-87.
  4. Komaroff AL. et al. (2021). Will COVID-19 Lead to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome? Front Med (Lausanne). 2021 Jan 18;7:606824. doi: 10.3389/fmed.2020.606824. PMID: 33537329; PMCID: PMC7848220.
  5. Kedor C. et al. (2022). A prospective observational study of post-COVID-19 chronic fatigue syndrome following the first pandemic wave in Germany and biomarkers associated with symptom severity. Nat Commun 13, 5104 (2022). https://doi.org/10.1038/s41467-022-32507-6.
  6. Grach SL. et al. (2023). Diagnosis and Management of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Mayo Clin Proc. 2023 Oct;98(10):1544-1551. doi: 10.1016/j.mayocp.2023.07.032. PMID: 37793728.