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After COVID vs after glandular fever

How ME/CFS that follows COVID-19 compares with ME/CFS that follows glandular fever (Epstein-Barr virus), and why some people develop it after an infection and others don't.

5 min read Last reviewed 8 November 2026

The same illness, different doors in?

ME/CFS can start after many different infections. Researchers think of the infection as a door into the illness. Once someone is through it, the illness tends to look similar regardless of how it started. Studies comparing people whose ME/CFS began after COVID-19 with people whose illness began earlier (often after glandular fever) have found very similar symptom patterns, including post-exertional malaise, brain fog, unrefreshing sleep and orthostatic intolerance. Observational

But there are some real differences, and they may matter for which treatments work.

Side by side

After glandular fever (EBV) After COVID-19
The virus Epstein-Barr virus, a herpes virus. It infects immune cells (B cells) and stays in the body for life, usually dormant. SARS-CoV-2, a coronavirus. It usually clears, but fragments of the virus have been found in some people’s tissues months later.
Who it typically affects Most often teenagers and young adults, the peak age for glandular fever All ages, most commonly adults aged 30–60. Women are more affected.
How often it leads to ME/CFS In a study of 301 US adolescents, about 13% met CFS criteria 6 months after glandular fever, 7% at 12 months and 4% at 2 years Observational1 Across all infected adults in the large US RECOVER study, 4.5% met ME/CFS criteria (versus 0.6% of uninfected people).2 Among people referred to a Berlin clinic with post-COVID fatigue, about 45% met ME/CFS criteria Observational3
Onset Often a clear start: a severe glandular fever illness that never fully resolves Can follow a mild infection. Some people develop symptoms after a second or third infection.
Extra symptoms more common Recurrent sore throats, tender glands, flu-like flares Breathlessness, chest pain, palpitations, loss of smell or taste, and clotting problems in some
Organ damage Uncommon Possible in some people: lungs, heart, blood vessels. These need to be checked for separately.
What researchers are looking at EBV reactivation, autoimmunity (EBV is also strongly linked to multiple sclerosis) Viral persistence, micro-clots, blood vessel damage, EBV reactivation (also seen in Long COVID)
Research funding Historically very low Much larger since 2020. Many new trials are in Long COVID.

EBV turns up in both stories:

  • EBV remains dormant in the body after glandular fever. Under stress, such as another infection, it can reactivate.
  • Several studies have found signs of EBV reactivation in people with Long COVID: one found it in 67% of Long COVID patients versus 10% of controls, and larger studies found EBV markers predicted who developed Long COVID. Observational4,5,6
  • EBV is known to trigger autoimmunity. In a study of 10 million people, the risk of multiple sclerosis rose 32-fold after EBV infection, which strengthens the case that it can set off long-term immune problems.7
  • That’s why the tests page recommends full EBV serology (VCA IgM and IgG, EBNA, early antigen), especially if your illness began after glandular fever.

Does the trigger change treatment?

Possibly, and researchers are paying attention:

  • Low-dose naltrexone: the 2026 Canadian placebo-controlled trial included only post-COVID patients and didn’t reach its goal. Griffith University’s lab work used classic ME/CFS patients. The results may not transfer between groups. See LDN.
  • Low-dose rapamycin: in the researchers’ preliminary analysis, people whose illness began after an infection responded better than those with non-viral onset. Open-label8
  • Johns Hopkins is directly comparing ME/CFS that began before the pandemic with ME/CFS that began after COVID.9 See trials.
  • Many trials only accept one group. Some Long COVID trials exclude anyone previously diagnosed with ME/CFS, while some ME/CFS trials exclude people whose illness started after COVID. Check eligibility carefully.

Why do some people get ME/CFS after an infection and others don’t?

Most people recover fully from glandular fever or COVID. Why do some go on to develop ME/CFS? Researchers talk about three kinds of factors.

1. What makes someone more vulnerable (predisposing)

  • Genes. DecodeME found eight genetic regions linked to ME/CFS, mostly in the immune and nervous systems.10 See Causes.
  • Sex. Women are affected around two to four times as often as men.11
  • Age. Onset peaks in adolescence and again in the 30s–40s.
  • Family history of ME/CFS or related conditions
  • Other conditions such as hypermobility (hEDS), allergies or autoimmune disease may play a part. Hypothesis

2. What sets it off (precipitating)

  • The infection itself, and especially how severe it was. The Australian Dubbo study followed 253 people after glandular fever, Q fever and Ross River virus. About 11% met criteria for chronic fatigue syndrome at 6 months, whatever the germ. The severity of the initial illness predicted who did, not their personality or mental health beforehand. Observational12
  • Repeated infections, such as COVID reinfection
  • Occasionally surgery, physical trauma or other major stress on the body

3. What keeps it going (perpetuating)

  • Pushing through too early. Many patients describe returning to work, study or exercise too soon after the infection, before a major decline. Patient surveys consistently report exertion as the main relapse trigger, though this is hard to study rigorously. Observational13
  • Repeated crashes from the boom-bust cycle
  • Poor sleep, untreated orthostatic intolerance or other untreated conditions
  • New infections

References

  1. Chronic fatigue syndrome after infectious mononucleosis in adolescents Observational
    Katz BZ et al., Pediatrics, 2009. 13%, 7% and 4% met CFS criteria at 6, 12 and 24 months
  2. Incidence and prevalence of post-COVID-19 ME/CFS: a RECOVER-Adult study Observational
    Vernon SD et al., Journal of General Internal Medicine, 2025. 4.5% of infected adults met ME/CFS criteria vs 0.6% of uninfected
  3. A prospective observational study of post-COVID-19 chronic fatigue syndrome following the first pandemic wave in Germany and biomarkers associated with symptom severity Observational
    Kedor C et al., Nature Communications, 2022. 19 of 42 patients referred with post-COVID fatigue (45%) met Canadian Consensus Criteria
  4. Investigation of long COVID prevalence and its relationship to Epstein-Barr virus reactivation Observational
    Gold JE et al., Pathogens, 2021. EBV reactivation in 67% of Long COVID patients vs 10% of controls
  5. Multiple early factors anticipate post-acute COVID-19 sequelae Observational
    Su Y et al., Cell, 2022. EBV viraemia was one of four factors predicting Long COVID
  6. Distinguishing features of long COVID identified through immune profiling Observational
    Klein J et al. (Putrino D, Iwasaki A), Nature, 2023. Low cortisol was the strongest single predictor of Long COVID status
  7. Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis Observational
    Bjornevik K et al., Science, 2022. Risk of MS rose 32-fold after EBV infection in more than 10 million people
  8. Low-dose rapamycin trial News
    Simmaron Research, 2026
  9. Blood-brain barrier integrity and immune dynamics in post-SARS-CoV-2 onset ME/CFS versus pre-pandemic ME/CFS (NCT07256795) Registry
    Johns Hopkins University (Azola A), ClinicalTrials.gov, 2026
  10. Initial findings from the DecodeME genome-wide association study of ME/CFS (preprint) Observational
    DecodeME Collaboration (Boutin T, Ponting CP et al.), medRxiv, 2025. Up to 15,579 cases vs 259,909 controls; eight loci; preprint, not yet peer reviewed as of September 2026
  11. Two age peaks in the incidence of chronic fatigue syndrome/myalgic encephalomyelitis: a population-based registry study from Norway 2008–2012 Observational
    Bakken IJ et al., BMC Medicine, 2014. Female-to-male ratio 3.2 to 1; incidence peaks at ages 10–19 and 30–39
  12. Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study Observational
    Hickie I et al. (Dubbo Infection Outcomes Study), BMJ, 2006. 11% met CFS criteria at 6 months; predicted largely by the severity of the acute illness
  13. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact Observational
    Davis HE et al., EClinicalMedicine, 2021. 86% of respondents reported relapses; exertion and stress were the main triggers