Long COVID clinical evaluation, research and impact on society: a global expert consensus, 2025, Ewing et al

[Nightsong]

Abstract:
Background
Long COVID is a complex, heterogeneous syndrome affecting over four hundred million people globally. There are few recommendations, and no formal training exists for medical professionals to assist with clinical evaluation and management of patients with Long COVID. More research into the pathology, cellular, and molecular mechanisms of Long COVID, and treatments is needed. The goal of this work is to disseminate essential information about Long COVID and recommendations about definition, diagnosis, treatment, research and social issues to physicians, researchers, and policy makers to address this escalating global health crisis.

Methods
A 3-round modified Delphi consensus methodology was distributed internationally to 179 healthcare professionals, researchers, and persons with lived experience of Long COVID in 28 countries. Statements were combined into specific areas: definition, diagnosis, treatment, research, and society.

Results
The survey resulted in 187 comprehensive statements reaching consensus with the strongest areas being diagnosis and clinical assessment, and general research. We establish conditions for diagnosis of different subgroups within the Long COVID umbrella. Clear consensus was reached that the impacts of COVID-19 infection on children should be a research priority, and additionally on the need to determine the effects of Long COVID on societies and economies. The consensus on COVID and Long COVID is that it affects the nervous system and other organs and is not likely to be observed with initial symptoms. We note, biomarkers are critically needed to address these issues.

Conclusions
This work forms initial guidance to address the spectrum of Long COVID as a disease and reinforces the need for translational research and large-scale treatment trials for treatment protocols.

Link | PDF (Ann Clin Microbiol Antimicrob 24:27, April 2025, open access)

 

[Utsikt]

Some of the statements:

Definitions:
Consensus level A statements:

The Long COVID definition should also include a criterion for significant functional impairment from baseline (including reduction in effort tolerance, even without additional new symptoms)

«Effort tolerance» is a very unfortunate description.

Acknowledging that many clinical phenotypes of Long COVID align with established syndromes such as post-intensive care syndrome, ME/CFS, and POTS, it is important to recognize that these conditions may have distinct pathophysiologic mechanisms

I don’t understand the purpose of the second half of this statement. If you get ME/CFS from covid, you have ME/CFS. I understand why it’s useful to be able to say that you have LC because it signifies the cause of your illness, but it doesn’t add any clinical value at this moment.

Long COVID is evident in young individuals with a documented history of SARS-CoV-2 infection, displaying at least one enduring physical, cognitive, or neuro-psychiatric symptom that persists for a minimum of 8–12 weeks after the initial infection, where other causes have been excluded

I’m not sure why this statement includes young people specifically.

It is important to recognize that Long COVID is an umbrella term encompassing several different disorders including e.g. dysautonomia, neuroinflammation, endothelial dysfunction, hypercoagulation, impaired fibrinolysis, mast cell disorders, and mitochondrial dysfunction. It is therefore important to establish a minimum Long COVID diagnostic workup for these conditions

I guess they wanted to mention all the buzzwords? And as per above, LC is not an umbrella term in the clinical sense. It just says what initially caused your illness.

Diagnosis and clinical assessment
Consensus level U statements

There is a need to educate all health care workers about the possible complications following SARS-CoV-2 infection and to ensure that patients are listened to, appropriately investigated and supported

100 % agree.

Consensus level A statements (not all of them)

Clinical assessment of Long COVID should examine the change in a person’s functional abilities from their previous baseline, as well as the cost of maintaining functioning (e.g. more effort and/or time required, and physical or cognitive exhaustion following tasks)

This seems to be mostly about PEF.

In diagnosing Long COVID patients it is important to screen for general symptoms including fatigue, post-exertional malaise (PEM)/post exertional symptom exacerbation (PESE), and persistent fevers

Are the equating PEM and PESE here?

In diagnosing Long COVID patients it is important to assess neurological/brain symptoms including sleep disruption, headache, seizures, cognitive dysfunction, mood changes, sensitivity to stimuli of the senses, hearing, vertigo, loss of smell/taste, dry eyes or mouth, temperature dysregulation, paraesthesia, changes in sweating, syncope, tremor/internal vibrations, hallucinations, depression and anxiety

This seems like a decent list for me personally, although it isn’t exhaustive.

In diagnosing Long COVID patients it is important to screen for orthostatic intolerance and dysautonomia, including postural orthostatic tachycardia syndrome (POTS)

In light of the critique of the concept of POTS, they could probably have left that out and just focused on OI. Dysautonomia also doesn’t tell us much.

Evaluation of all aspects of Long COVID should account for the fluctuating nature of many symptoms and recognise the need for repeated measurements to capture clinical findings (e.g. autonomic dysfunction, cognitive difficulties)

Important point!

It is important that clinicians realise that most standard screening tests will come back normal and specific tests are needed for diagnosis of various pathologies in Long COVID

Important point!

Clinically validated Long COVID-specific biomarkers, when available, will play a role in diagnosing Long COVID, despite its complexity

We’ll never get an LC biomarker. But we might get biomarkers for certain aspects of the issues that covid can cause.

Evaluation for neuropsychiatric manifestations, such as anxiety, depression, sleep disturbance, cognitive disturbance, and/or ADHD should be part of a comprehensive assessment of Long COVID patients

Technically yes, but many of those evaluations will give false positives for anyone with a chronic illness. So they can’t be used as explanations for the symptoms.

 

[Utsikt]

Treatment
Consensus level A statements (some of them)

Multidisciplinary teams (MDTs) are a useful model for care of Long COVID

Based on what?

Treatments should be tailored to the history and clinical examination

What’s the alternative? MDTs?

Psychological therapies can be useful in supporting the mental health of those with Long COVID in conjunction with treatments that target the pathophysiology

I disagree. Psychosocial support can be useful. Treatment not so much unless for specific problems.

Evaluation of treatment
Consensus level B statements

The Symptom Burden Questionnaire for Long COVID (SBQ-LC) can be used to monitor the effect of treatment in patients with Long COVID

That’s this, and I’m not sure how this can be used to monitor the effect of treatments.

If determined safe and appropriate following detailed screening for post-exertional malaise (PEM), repeat cardiopulmonary exercise testing (CPET) can be important to monitor changes in VO2 max and anaerobic threshold and to measure the effectiveness of treatments (including rehabilitation programmes) in Long COVID

This section really just says X can be useful for monitoring the effect of treatments. But it seems to me like that would depend on what you’re trying to treat in the first place?

 

[SNT Gatchaman]

NZ newsroom: NZ’s Long Covid blind spot nothing short of a crisis
Anna Brooks, PhD (S4ME: @DrAnnaNZ)

[…] a global consensus on Long Covid has just been published, the first to bring together clinicians, researchers, and people with lived experience from 28 countries. I represented Aotearoa New Zealand as part of the lead authorship team shaping a shared framework to better understand one of the most significant and lasting consequences of the Covid-19 pandemic.

Although not a definitive guide, this paper marks the first time such a broad, interdisciplinary group has aligned on clinical, scientific, and structural approaches to Long Covid. As a researcher focused on immune dysfunction and post-infection syndromes, I see this paper as a crucial first step, a foundational framework to unify efforts, guide research priorities, and support future advances in science and care.

While Long Covid has brought overdue attention to the long-term health consequences of infections, this phenomenon is not new. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) has long been recognised as a serious post-infection syndrome.

This isn’t merely feeling tired; it is debilitating exhaustion, often described as feeling ‘poisoned’, triggered even by minor exertion such as walking a few metres, and persisting for days or weeks. Unfortunately, no diagnostic tools currently exist to detect this dysfunction, medically termed post-exertional malaise. Developing such a diagnostic tool would finally provide the objective validation that patients have been missing for decades.

Recognising post-exertional malaise is critical, not just for accurate diagnosis but to prevent harm. Pushing through physical activity can worsen the underlying energy dysfunction – a phenomenon now clearly documented in scientific literature, and a risk widely acknowledged by clinical experts.

Both Long Covid and ME/CFS are under-recognised, not because they are rare, but because clinicians lack the tools and training to adequately detect the systemic dysfunction they reflect, a gap that only investment in research and better clinician education can address.

The paper highlights areas where research is urgently needed. This includes how the immune system, nervous system, cellular energy and metabolism, and gut microbiome may all be involved

The global consensus paper signals emerging international scientific alignment on Long Covid and highlights the research and care gaps that demand urgent attention. What we need now is targeted research and a strategy to disseminate and educate our healthcare workforce – so we can develop the tools needed to prevent, diagnose, and care for people effectively. This consensus marks an essential starting point for action.

After all, post-infection syndromes are not new – but pandemic-scale waves of a novel virus exposed just how ill-prepared we were to recognise and respond to them. Covid-19 continues to drive long-term illness, and if we fail to invest in research and recognition now, the burden will only deepen. We must act urgently – not only to prepare for future pandemics, but to confront the growing crisis we are already facing.

 

[Utsikt]

This isn’t merely feeling tired; it is debilitating exhaustion, often described as feeling ‘poisoned’, triggered even by minor exertion such as walking a few metres, and persisting for days or weeks. Unfortunately, no diagnostic tools currently exist to detect this dysfunction, medically termed post-exertional malaise. Developing such a diagnostic tool would finally provide the objective validation that patients have been missing for decades.

Unfortunate that there is no mention of delay. And PEM is not just exhaustion. It’s not very encouraging to see so basic mistakes by the experts that have been involved.

Recognising post-exertional malaise is critical, not just for accurate diagnosis but to prevent harm. Pushing through physical activity can worsen the underlying energy dysfunction – a phenomenon now clearly documented in scientific literature, and a risk widely acknowledged by clinical experts.

I don’t think anyone has proven an underlying energy dysfunction, or that it’s central to PEM, or that it worsens as a result of PEM.

Both Long Covid and ME/CFS are under-recognised, not because they are rare, but because clinicians lack the tools and training to adequately detect the systemic dysfunction they reflect, a gap that only investment in research and better clinician education can address.

I disagree. It’s under-recognised because clinicians don’t listen to patients.

Endometriosis shows how having an objective biomarker doesn’t automatically lead to earlier detection if clinicians still dismiss the patients.

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I know I’m being critical here, but we have to get these things right if we are going to try to solve the problems.

 

[Nightsong]

"Trial By Error: Andrew Ewing & David Joffe on Just-Published “Global Expert Consensus” on Long Covid":

https://virology.ws/2025/05/02/tria...lished-global-expert-consensus-on-long-covid/

Includes a video interview with two of the authors.