Comparing ME/CFS following mononucleosis with Long COVID, 2026, Jason et al

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Comparing ME/CFS following mononucleosis with Long COVID

Jason, Leonard A; Furst, Jacob; Katz, Ben Z

Objectives
Long COVID following SARS-CoV-2 and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) following infectious mononucleosis (IM) are examples of post-infectious chronic illnesses. Behavioral and pathophysiological underpinnings of both ME/CFS following IM and Long COVID are not well understood.

Methods
We studied ME/CFS development following IM in a diverse group of college students who were enrolled before the onset of IM. We categorized those meeting either moderate or severe ME/CFS criteria.

We subsequently recruited a matched sample of those infected with SARS-CoV-2, some of whom recovered and others of whom developed Long COVID. We compared and contrasted ME/CFS and Long COVID following IM and SARS-CoV-2 infection in terms of somatic symptoms, coping strategies, depression and anxiety symptoms, and functional status.

Results
In general, the Long COVID group's symptom burden was less than that of the Severe ME/CFS group but more than that of the Moderate ME/CFS group.

Discussion
These findings may allow investigators a better understanding of these post-viral illness pathophysiologies.

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This compares their previous 2014-2018 glandular fever cohort to an LC cohort who

were recruited in 2023-2024 by social media sources and from posters and recruitment efforts at local universities

The participants were given

a medical evaluation, and that, along with self-report questionnaires (see below) helped determine whether a person had recovered or not from SARS-CoV-2. Those classified as Long COVID had continuous, relapsing, and remitting symptoms affecting one or more organ symptoms for at least three months following acute SARS-CoV-2 infection.1

Matching occurred on sex, race, ethnicity, and age for those 55 with ME/CFS following IM, the 55 with Long COVID, the 62 Controls who recovered from Mono and the 62 controls who recovered from SARS-CoV-2

There are pages of data tables comparing the ME/CFS and LC groups on various metrics. They used DSQ, SF-36, Compass-31, the Perceived Stress Scale, the Modifiable Activity Questionnaire, the Fatigue Severity scale, a 'Coping Orientation to Problems Experienced' Scale, and the Beck Depression Inventory. A few brief quotes from the summary of results ("Severe ME/CFS" here means those who met >1 set of criteria):

The Long COVID group had 18 significantly higher frequency/severity of symptoms than the Moderate ME/CFS group, including post-exertional malaise, Sleep, Neurocognitive, Neuroendocrine, Pain, and Autonomic domains; only in the Immune and Gastrointestinal domains were there no significant differences. It was more difficult to differentiate patients with Long COVID symptoms from those with Severe ME/CFS, but the latter group was more impaired in the following domains: Sleep (“needing to nap”), Immune (“sore throat” and “tender lymph nodes”), and Gastrointestinal (“abdomen/stomach pain”).

Although the Long COVID group had more physical functioning limitations and worse scores on anxiety and use of denial than the moderate ME/CFS groups, for almost all the other measures in Table 3, there were no significant differences, suggesting that while symptomatology does vary across the groups, functioning, coping, autonomic dysfunction, fatigue and stress were comparable. When differences did occur, they tended to be between the Long COVID and Control groups, with fewer differences between the ME/CFS groups and the Controls, and this is particularly apparent in the areas of coping.

In summary, the Long COVID group has less symptomatology than the Severe ME/CFS group, while the Long COVID group in comparison to the Moderate ME/CFS group had more symptoms, physical functioning reductions, and were more likely to have anxiety and use of denial as a coping mechanism.