Persistent fatigue. Brain fog. Poor sleep. Dizziness on standing. Symptoms that worsen days after even mild exertion.

For some doctors the pattern is still difficult to interpret. For others it has become increasingly recognisable. It is the evolving clinical picture of long COVID.

Years after the pandemic began, the condition continues to challenge clinicians across multiple specialties. Researchers are beginning to identify possible biological mechanisms, but diagnosis remains largely clinical and treatment options are still evolving.

Exactly how many people develop long COVID is still uncertain.

Dr Oyuka Byambasuren, Assistant Professor of Evidence-Based Medicine at the Institute for Evidence-Based Healthcare at Bond University, is involved in several Australian long COVID studies. She said even conservative estimates suggest the country is facing a substantial burden.

“With roughly 15 million Australians having had COVID-19 at least once, even relatively modest prevalence rates mean hundreds of thousands of people may have experienced long COVID,” she told the limbic.

Dr Emma Tippett, an infectious diseases physician and long COVID specialist, said the true number of Australians affected is difficult to pin down.

“Some estimates suggest around 400,000 Australians are living with long COVID. Other estimates suggest the number could be closer to one million,” she said.

That would make the condition between 10 and 100 times more common than multiple sclerosis, she points out.

“And we know a lot about MS. Most clinicians could diagnose MS. But we know very little about long COVID.”

What is even harder to measure, she added, is how many people’s lives have been dramatically reshaped by the illness.

“What we don’t know is how many of those people are housebound or unable to work.”

At her clinic, the impact on patients’ working lives is often striking.

“We know that about 90% of our patients have had to modify their work because of long COVID,” she said.

Building a clinic to fill the gap

Dr Tippett became involved in long COVID care early in the pandemic.

Recognising that many patients with prolonged symptoms had nowhere to go, she established Clinic 19, a national telehealth

service designed to support people with the condition.

“It became clear very early on that COVID was going to leave a lot of people absolutely devastated,” she said.

“And there were very few options for care in Australia.”

Since launching in 2022, the service has grown into a multidisciplinary clinic drawing on specialists across multiple fields.

“We’ve gathered a team of 18 specialists who are willing to tackle long COVID,” she said.

The clinic has now seen more than 1,600 patients from across Australia and New Zealand, including children.

Yet as specialist services established earlier in the pandemic begin to disappear, the fact that the country’s largest long COVID clinic operates privately highlights what Dr Tippett sees as a deeper structural gap in the health system.

“The largest remaining long COVID clinic – and the only dedicated paediatric service – should not be a private enterprise,” she said.

An invisible condition 

Part of the challenge, Dr Tippett said, is that long COVID is largely invisible.

“Because it’s invisible, we can’t measure it properly,” she said. “And if we can’t measure it, we can’t provide the care people need.”

Recognition of the condition among clinicians has improved since the early stages of the pandemic. But patients, she said, often still struggle to find doctors with experience managing it.

“Even though most medical professionals now accept that long COVID is a real disease, patients still encounter medical trauma when they seek care,” she said.

“They are often sent to ten different specialists, most of whom don’t know what to do with long COVID – they’re not experienced in it and they’re not comfortable managing it.”

One misconception she often encounters is the belief that little can be done once long COVID develops.

“The biggest mistake doctors make is assuming there’s nothing they can do,” she said.

“We were taught early on that the main treatment was time – that people would get better without intervention. But that’s not true.”

Recognising the clinical picture

Researchers are gradually beginning to identify patterns in who is most likely to develop long COVID, although the risk profile remains far from definitive.

Women appear to be disproportionately affected, accounting for roughly two-thirds of cases in several studies, a pattern noted across multiple international cohorts, explains Professor William Rawlinson, a senior medical virologist and director of the Serology, Virology and OTDS Laboratories (SAViD) at NSW Health Pathology.

People who experienced more severe acute infections – particularly those requiring hospitalisation or intensive care – also appear to face higher risk.

Meanwhile, certain underlying health conditions, including asthma, cardiovascular disease, diabetes, obesity and smoking, have been linked to more persistent symptoms.

Some studies have also suggested that people with personal or family histories of post-viral illnesses such as myalgic encephalomyelitis or chronic fatigue syndrome may be more vulnerable, he adds.

Yet clinicians caution that these risk factors offer only partial guidance. Many patients who develop long COVID were previously healthy and experienced only mild initial infections, highlighting how much remains unknown about why the condition develops in some people but not others.

“The epidemiological risk factors we talk about – age, comorbidities and so on – are not always very helpful when looking at an individual patient,” Professor Rawlinson said.

“Most people with long COVID do have some risk factors, but many people with those same risk factors never develop long COVID. So epidemiology does not always help much when managing individual cases.”

Many of the patients arriving at Dr Tippett’s clinic had previously been healthy and highly functional.

“The patients I see are not who you might imagine when you think about chronic illness,” she said.

“They were fit, healthy and productive before COVID. Our patients include healthcare workers, teachers, lawyers, cleaners and even elite athletes.”

One feature, she said, is particularly important for clinicians to recognise – post-exertional malaise.

“This is a cardinal feature that needs to be understood when managing people with long COVID.

“People are overwhelmingly fatigued, but if they push through an activity – physical, emotional, cognitive or even social – and go beyond what I call their post-exertional malaise threshold, their symptoms become much worse.”

The deterioration is often delayed.

“That worsening is usually delayed by a day or two and can take days or weeks to recover from.”

Understanding that pattern is critical when considering rehabilitation strategies, she said.

“This is why pushing through symptoms and graded exercise therapy can actually be harmful in long COVID. There is a limit to what someone with long COVID can do before they start harming themselves.”

Many patients also experience cognitive dysfunction, commonly described as “brain fog”, alongside unrefreshing sleep that compounds fatigue.

Autonomic dysfunction is another frequent feature.

A significant proportion of patients develop postural orthostatic tachycardia syndrome, or POTS, where the body struggles to regulate heart rate and blood pressure when standing. Patients may experience dizziness, palpitations and difficulty remaining upright for long periods.

Researchers studying long COVID cohorts are beginning to identify recurring patterns.

Professor Byambasuren said more than 200 symptoms have been described in the literature, but several clusters appear repeatedly.

“These include fatigue-dominant illness with post-exertional symptom exacerbation, autonomic dysfunction, mast-cell activation syndromes and neurocognitive symptoms,” she said.

Many patients experience features of several clusters at once.

“What we are increasingly seeing is that long COVID is not one condition but several overlapping syndromes.”

That complexity can fragment care, she said, leaving patients navigating multiple specialists without clear pathways.

Inside a long COVID consultation

A first appointment at Clinic 19 typically lasts about 50 minutes.

Before the consultation begins, patients are asked to complete a detailed four-page questionnaire covering the wide range of symptoms reported in long COVID.

Much of the appointment is spent reconstructing the timeline of symptoms.

“We spend a lot of time going through the history – when the infection happened, what symptoms started when, and how they’ve changed over time,” Dr Tippett said.

Rather than focusing on a single diagnosis, the consultation shifts towards understanding how the illness is affecting daily life.

“It’s not just about listing symptoms, it’s about understanding what people can and can’t do anymore,” she said, adding that many patients arrive worried their symptoms will not be taken seriously.

Emerging approaches to management

There is still no definitive treatment for long COVID. But clinicians are beginning to experiment with approaches aimed at particular symptom clusters.

One medication attracting increasing attention among clinicians managing long COVID is low-dose naltrexone, a drug traditionally used in addiction medicine but increasingly explored for its potential anti-inflammatory and neuro-immune effects.

Dr Tippett said the medication can be particularly helpful for patients struggling with fatigue and cognitive dysfunction.

At her clinic, doses typically range from around 3 mg to 12 mg, with responses varying between patients.

Data from around 120 patients treated at her clinic suggests more than 75% reported some improvement, although responses ranged from marginal benefit to substantial functional gains.

“For most people it’s the difference between feeling terrible all day and not being able to do anything – and still not being able to do much, but not feeling terrible while they’re doing it,” she said.

Management of autonomic dysfunction, particularly POTS, is another area where relatively simple measures can improve symptoms.

In many cases this begins with increased salt intake, compression garments and medications such as ivabradine.

Patients may still experience fatigue or post-exertional malaise, but improving orthostatic tolerance can significantly increase daily functioning, Dr Tippett said.

“You start with those measures and if that doesn’t manage it, then you can consider further referrals. But those basic measures will help the majority of people with POTS.

They can significantly improve people’s functional capacity and the amount of time they can spend upright. They may be able to stand up and cook dinner, or get through a shower without collapsing. They get fewer headaches. They just generally feel a bit better and can do more,” she said.

Part of the hesitation among doctors, she said, stems from the complexity of the condition. Symptoms are often difficult to measure using conventional investigations and may be dismissed as anxiety or functional illness.

But she said clinicians should not assume the condition is untreatable.

“If clinicians can move past that mindset, and start with some simple steps – looking for POTS, being open to prescribing low-dose naltrexone, optimising sleep – they’ll already be doing their patients a big service.

“And because the symptoms are so varied, if a patient presents with a broad range of new issues, it’s worth asking whether they could be related to a previous COVID infection.”

Diagnosing a complex condition

Despite the diagnostic challenges, Professor Rawlinson said one point is clear.

“There is no doubt that it is a real disorder.”

He said the main difficulty lies in the absence of a single diagnostic test.

Before diagnosing long COVID, clinicians must rule out a wide range of alternative conditions.

These include endocrine disorders such as hypothyroidism, autoimmune diseases such as systemic lupus erythematosus, cardiac complications including myocarditis, and chronic respiratory diseases like asthma or COPD.

When no other explanation is found, the diagnosis becomes post-acute sequelae of SARS-CoV-2 infection, he said.

First attempts to synthesise the evidence

For several years clinicians managing long COVID have relied largely on emerging clinical experience rather than formal evidence.

That experience is now beginning to be reflected in the first international attempts to synthesise research on the condition.

A new clinical practice guideline published in the European Respiratory Journal [link here] reviews the available evidence across the major manifestations of long COVID.

Pulmonary complications remain one of the most common and clinically significant aspects of the illness, particularly in patients who experienced severe respiratory disease during the acute phase of infection, the review states.

Long-term abnormalities in lung imaging and pulmonary function – including impaired diffusing capacity – have been documented months and even years after infection.

Yet treatment options remain limited.

According to the guideline working group, randomised trials exploring antivirals such as nirmatrelvir–ritonavir have not demonstrated meaningful improvements in established long COVID. Evidence supporting monoclonal antibodies is similarly sparse, while routine glucocorticoid therapy is discouraged because potential harms may outweigh uncertain benefits, they advised.

Instead, the guideline recommends symptom-directed care and carefully supervised rehabilitation.

Structured rehabilitation programs may improve breathlessness and exercise tolerance in some patients, but clinicians are advised to assess carefully for post-exertional symptom exacerbation before recommending exercise.

For patients whose symptoms worsen after exertion, pacing and activity management may be more appropriate.

The guideline also examines probiotics, which have attracted attention because of emerging research linking the gut microbiome to immune regulation. Small studies suggest possible improvements in respiratory symptoms, but the evidence remains too inconsistent to support routine clinical use, they wrote.

Cognitive behavioural therapy may help some patients manage fatigue and psychological symptoms, although the evidence remains low certainty and CBT is considered an adjunctive therapy rather than treatment for the underlying condition.

Research priorities

For Professor Byambasuren, one of the central challenges now is translating emerging research into practical care.

Following the federal parliamentary inquiry into long COVID, the Australian government committed about $50m to research.

But she said much of that funding has focused on models of care rather than clinical trials of treatments.

“At the moment very little funding has gone toward testing therapies that might actually improve patients’ symptoms,” she said.

Her research group is now working on projects aimed at strengthening GP-led care.

One initiative, the BEACON project, aims to support general practitioners managing long COVID through specialist telehealth advice and shared clinical expertise.

“In practice, effective care usually has a primary care anchor,” she said.

“A GP coordinates the overall management plan, while specialist referrals are targeted to specific problems.”

The future of care

For Dr Tippett, the larger question is how health systems respond to the growing number of people living with the condition.

She argues Australia needs a coordinated national approach.

There is growing pressure for long COVID care to be absorbed into general practice, but expecting primary care to manage the condition alone is unrealistic, she said.

“I think that’s really difficult to ask primary care to take this on entirely.

I spend about an hour with a patient. They have so many symptoms and it’s so complex. We’re thinking about long COVID all day, every day. We’re gathering feedback from patients as they try new medications. We have the time to read the research papers because this is what we do.

I just don’t think you can expect GPs to do that on top of everything else.”

Among the measures she believes would make the greatest difference are publicly funded multidisciplinary clinics capable of supporting patients with long COVID, ME/CFS and dysautonomia.

Access to treatment is another barrier. Many medications used in specialist clinics are prescribed off-label and are not subsidised through the Pharmaceutical Benefits Scheme.

Speaking at a parliamentary inquiry into long COVID, Dr Tippett said governments should consider subsidising some therapies while clinical trials are still underway.

“Providing emergency approval to subsidise off-label medications – in particular low-dose naltrexone, ivabradine and midodrine – without waiting for clinical trials.”

Ultimately, she said, the response to long COVID will shape how health systems respond to future pandemics.

“What we build now will determine how we respond to the next pandemic,” she said.

Respiratory viruses have long been capable of triggering prolonged illness in a subset of patients.

“If we build the infrastructure – specialist clinics, diagnostic tools, trained clinicians and treatments – we will be far better prepared when the next virus arrives.”