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 US college students, about 13% met CFS criteria 6 months after glandular fever, 7% at 12 months and 4% at 2 years Observational | At a Berlin clinic, about 45% of people still unwell with moderate to severe fatigue after COVID met ME/CFS criteria Observational |
| 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. |
Epstein-Barr virus: the link between them
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, and it’s been linked to Long COVID fatigue. Observational
- EBV is known to trigger autoimmunity. It’s the main risk factor for multiple sclerosis, which strengthens the case that it can set off long-term immune problems.
- 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: people whose illness began after an infection responded better than those with non-viral onset. Open-label
- Johns Hopkins is directly comparing ME/CFS that began before the pandemic with ME/CFS that began after COVID. 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. See Causes.
- Sex. Women are affected around three times as often as men.
- 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 people after glandular fever, Q fever and Ross River virus. About 1 in 10 developed a lasting post-infective fatigue syndrome, whatever the germ. The severity of the initial illness predicted who did, not their personality or mental health beforehand. Observational
- 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 this, though it’s hard to study rigorously. Observational
- Repeated crashes from the boom-bust cycle
- Poor sleep, untreated orthostatic intolerance or other untreated conditions
- New infections