Patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or long COVID often describe a life that has narrowed, long after an infection has resolved. This includes reduced capacity, difficulty recovering after exertion and symptoms that cross over into multiple systems.

For clinicians, recognising the pattern early can prevent years of deterioration.

As the evidence base has evolved, so has out understanding of clinical presentation. Here’s an overview of current best practice for diagnosing and managing ME/CFS and long COVID – with some myth-busting along the way.

Myth 1: ‘Because there’s no biomarker, we can’t confidently diagnose ME/CFS’

Fact: Absence of a single confirmatory test does not mean that illness does not exist. 

Conditions such as migraine, early-stage Parkinson’s, irritable bowel disease, and psychiatric conditions are regularly diagnosed without laboratory tests – and broken bones existed before X-rays. Disease exists regardless of our ability to visualise or measure it.

The key is identifying a clinical pattern.

ME/CFS and long COVID are diagnosed based on clinical criteria, specifically the nature and duration of the symptoms associated with functional decline and critically, the presence of post-exertional malaise (PEM)

The biology behind ME/CFS

ME/CFS is a multi-system illness involving immune system, autonomic system, metabolic and neurological dysfunction.

Autonomic dysfunction

The patient may present with palpitation, dizziness, orthostatic intolerance and worsening symptoms when standing. 

Neurological dysfunction

This can include ‘brain fog,’ difficulty concentrating, very slow processing ability and sensory overload.

Immune and metabolic dysfunction

Patients often describe flu-like symptoms that won’t go away, and very poor tolerance to exertion, like a battery that can never fully charge.

Mitochondrial dysfunction may play a role, but the biology is heterogeneous.

Where does long COVID fit into it?

 A substantial proportion of people with long COVID develop a clinical phenotype that overlaps with ME/CFS. In our clinic, about 80% of long COVID patients fit the criteria for ME/CFS, particularly those with post-exertional malaise, unrefreshing sleep, cognitive impairment and orthostatic intolerance. The pathophysiology for long COVID is the same as for ME/CFS, as the same management principles apply.

Myth 2: ‘Investigations are normal so it must mean nothing is wrong’

Fact: Normal results don’t mean function is normal. The average diagnostic delay is 10 years, according to the ME/CFS support organisation Emerge Australia.

Normal blood tests and imaging help exclude some of the alternative explanations, but ME/CFS (and long COVID) is diagnosed based on the clinical pattern and timing, particularly the relationship between exertions and delayed symptoms worsening – or PEM.

ME/CSF is no longer a diagnosis of exclusion. It is an active diagnosis based on clinical criteria.

The NAM diagnostic criteria

The US National Academy of Medicine criteria require:

• Substantial reduction in pre‑illness function for ≥6 months
• Post‑exertional malaise
• Unrefreshing sleep
• Either cognitive impairment OR orthostatic intolerance

Symptoms must be present at least half the time and of at least moderate severity.

It should be noted that symptom type and severity can fluctuate quite widely, so it’s important to look at the past month, rather than the last day.

Key questions to ask:

• What can the person do now compared to before?
• How long does it take them to recover?
• Can they work, shop, prepare meals, care for children, socialise etc — and what happens afterwards?

Practice tip: Check the clinical criteria and timeline to see if there has been a substantial reduction of their pre-illness function. Ask specifically about post-exertional malaise (PEM), sleep, cognitive impairment and orthostatic symptoms.

Rather than just listing symptoms, also clearly document functional decline. The WHO Disability Assessment Schedule is one tool that can help quantify this, and is important for NDIS, Centrelink and insurance.

Avoid indiscriminate testing

First-line investigations include full blood count, urea and electrolytes, iron studies, B12, folate, thyroid and ANA screen if autoimmune features are present.

Other tests may also be indicated if there is a good clinical reason – for example a NASA Lean Test to screen for POTS /OI, ECG, holter and/or echo to look for OI/ cardiovascular causes or sleep studies to rule out OSA or other sleep related causes.

However, ordering increasingly obscure tests without indication does not improve diagnostic accuracy. Don’t pursue extensive panels without clinical features.

Start supportive management while investigations are underway, and remain alert that comorbidities can occur. Supportive management refers to pacing, or energy conservation, and treating symptoms that are causing the most issues such as sleep, pain, OI or those related to a co-occurring condition.

Identifying post-exertional malaise (PEM)

Key questions to ask:

• Do symptoms get worse after even mild physical or cognitive effort? Is there a delay before the worsening occurs? (e.g. 12-48 hours after the activity?)
• How long does it take to recover? (Hours, days or longer?)
• Does the patient have to pace themselves to prevent a crash?
• Has pushing through cause further deterioration?

Sometimes the crash happens a few hours or even a day or two later.  For example, the person sitting in front of you in your clinic may appear functional, but even attending the appointment itself can have consequences in the days after that you won’t see.

Myth 3: Patients should gradually increase their physical activity

Fact: While this advice is appropriate for other conditions, it provokes crashes when PEM is present.

If PEM is suspected, advise the patient not to push themselves while assessments continue. They should pace themselves.

PEM is different from deconditioning

PEM involves delayed, multi‑system deterioration — often hours or days later — affecting cognition, sleep, pain and flu‑like symptoms. This pattern is not seen in uncomplicated deconditioning, where recovery is proportional to exertion and tolerance improves with training.

Deconditioning can occur secondary to ME/CFS, but PEM must be stabilised before any rehabilitation is attempted and can create real limits in terms of how much function is regained.

Exercise guidance

It’s important to match activity levels to the patient’s current capacity.

The 2021 NICE guidelines for ME/CFS advise against graded exercise therapy (GET) or fixed incremental increases in physical activity.

Energy management and pacing are crucial.

Pacing

Pacing means matching activity to current capacity to reduce PEM. It requires understanding the patient’s energy envelope and balancing physical, cognitive, emotional and social activities.

It can be helpful to explain to patients that their body currently has a smaller and sometimes unpredictable energy budget, and every activity draws on this budget. Thinking, standing, working, talking — they all come from the same budget. If you repeatedly spend more than you have, you will have it will lead to crashes.

A practical starting point is to aim to use 70–80% of capacity to leave some “energy in the budget”

Strategies include symptom diaries, heart‑rate tracking, planned rest breaks and spacing high‑demand activities.

Good pacing often requires external support such as workplace adjustments, household help, school accommodations, mobility aids or OT involvement.

Myth 4: It’s just a mental health issue

Fact: There are often overlapping symptoms, but ME/CFS has criteria that distinguish it from mental health disorders

A mental health history should not explain all symptoms.

Me/CFS and mental health disorders can co-exist. Mental health conditions can predate the illness, arise alongside it, or develop.

Fatigue, poor sleep and reduced activity occur in both, but PEM, orthostatic intolerance, flu‑like symptoms and sensory sensitivity point toward ME/CFS.

Clinicians should validate the patient’s experience, and also make a careful differential diagnosis.

Practice tip: The 2021 NICE guidelines state that CBT is not curative, though it may be used as a supportive therapy.

Physical assessment is important even if you suspect there may also be a psychological contributor.

On the flipside, it’s important not to attribute everything to ME/CFS long COVID.

Red flags to watch for include worsening hypoxia, syncope or severe syncope, cardiac chest pain, focal neurological symptoms, progressive confusion, and significant inflammatory or coagulation abnormalities. 

Ask if the symptom is consistent with the patient’s usual symptom pattern. If there’s something new or more severe or different, it should be assessed.

Myth 5: An ME/CSF diagnosis will ruin their life

Fact: There’s also a risk of not diagnosing

Without a diagnosis the patient will continue to have these crashes and deteriorate further because they continue to push instead of pacing themselves. Their symptoms are also not taken seriously, and sub optimal symptom management contributes to reduced function and quality of life.

The functional impairment already exists and the diagnosis gives the person a chance to learn about the condition and receive appropriate support including belief from friends, family and healthcare professionals.

Key takeaways:

• Post‑exertional malaise should be identified before prescribing activity
• Document functional decline clearly
• Provide pacing advice as a deliberate clinical intervention
• Avoid phrases such as ‘try to do a bit more every day,’ ‘your tests are normal so you’re fine,’ and ‘exercise will give you more energy.’

For more information

Emerge Australia – National Australian not-for-profit organisation for information, support and advocacy about myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)