The State of Chronic Fatigue: A Systematic Review of Current Contributors and Underpinnings to Post-exertional Malaise, 2026, Kuns et al

[Dolphin]

https://www.archives-pmr.org/article/S0003-9993(26)00547-2/abstract

Systematic & Meta-analytic Review Poster 3189116Volume 107, Issue 5e191May 2026

The State of Chronic Fatigue: A Systematic Review of Current Contributors and Underpinnings to Post-exertional Malaise​

Monica Coran Kuns ∙ Ava-Kathleen Rybicki ∙ Alba Azola ∙ Josefina Casamento-Moran ∙ Sruthi Kundur ∙ Humbal Omar ∙ Akshay Peddireddy ∙ Peter Rowe ∙ Agostina Casamento-Moran Show less
Affiliations & Notes

Article Info
DOI: 10.1016/j.apmr.2026.02.468


Show Outline

Abstract​

Objective(s)​

To identify the current evidence on neurobiological mechanisms of post-exertional malaise (PEM) and post-exertional symptom exacerbation (PESE) in individuals with Long Covid and/or myalgic encephalomyelitis/chronic fatigue syndrome following emotional, cognitive, or physical activity.

Data Sources​

An article search was completed across six databases including: PubMed, Embase, World Health Organization, Scopus, and Web of Science. Some keyword search terms include Long Covid, ME/CFS, Chronic Fatigue Syndrome, myalgic encephalomyelitis, and post-exertional malaise.

Study Selection​

Title and abstract reviews identified articles meeting inclusion criteria for full text review. Abstract exclusion criteria included cross-sectional studies only looking at one timepoint, any articles documenting another population without comparison to ME/CFS and/or Long COVID cohorts, pediatric populations, reviews, meta-analyses, and opinion papers. Reviewers selected 205 articles. Four pairs of two reviewers independently reviewed each complete article using the following inclusion criteria: target population of Long Covid or ME/CFS, >18 years old, outpatient setting, completion of any emotional, cognitive, or physical activity, presence of PEM, and at least pre and post activity measurements. Articles that did not meet the inclusion criteria were excluded, yielding a final sample of 79 articles for analysis.

Data Extraction​

Data extraction from each article was completed by two reviewers independently to ensure accuracy. The data identified included study details such as location and study design; cohort information including inclusion/exclusion criteria, age, disease duration; activity presented including timeframes and task intensity; outcome measures collected; and final results.

Data Synthesis​

Extracted data was classified according to study design, frequently used activities to elicit PEM, and common outcome measures. Standard physical assessments used to assess for PEM were the CPET and grip strength, frequently completed across two timepoints. Data revealed inconsistencies in the evaluated biomarkers and physical markers evaluated. Additionally, less than ten studies incorporated emotional and cognitive tasks as a means of inducting a PEM episode. Likewise, less than ten studies held the participants for more than 24 hours following PEM episode.

Conclusions​

While emotional and cognitive exertion are documented as contributing factors to PEM, activities eliciting these forms of exertion in addition to or instead of physical effort are rarely included. Multiple biological outcomes may be assessed to better understand the underpinnings of PEM. Improved understanding of this etiology and accessible techniques to elicit/monitor PEM within various functional activities remain necessary within the current literature. Further research is needed to not only understand the biological mechanisms of PEM, but the post-episodic biologic pathways to recovery as well.

Key Words​

1. Post-exertional malaise
2. Chronic Fatigue Syndrome
3. Myalgic Encephalomyelitis
4. ME/CFS
5. Long Covid

 

[Hutan]

That's an odd abstract. The only affiliation listed for all the authors is GSPP Rehabilitation, which is the therapy provider for Penn Medicine. Peter Rowe is included there, and I assume it is the same Peter Rowe who is an ME/CFS and orthostatic intolerance researcher and clinician. The Journal is Archives of Physical Medicine and Rehabilitation.

I don't think it's an accident that 'emotional activity' is mentioned first here and highlighted generally.

following emotional, cognitive, or physical activity.

target population of Long Covid or ME/CFS, >18 years old, outpatient setting, completion of any emotional, cognitive, or physical activity

Additionally, less than ten studies incorporated emotional and cognitive tasks as a means of inducting a PEM episode.

While emotional and cognitive exertion are documented as contributing factors to PEM, activities eliciting these forms of exertion in addition to or instead of physical effort are rarely included.

Further research is needed to not only understand the biological mechanisms of PEM, but the post-episodic biologic pathways to recovery as well.

I guess we can look forward to research into emotional stressors as precipitators of PEM. Which, is probably a valid thing to research, hopefully though the researchers aren't too biased.

 

[Hutan]

Monica Coran Kuns is a speech therapist.

She co-authored this study last year

Speech Therapy in the PASC/Long COVID Population: Implementation of a Structured Treatment Approach to Improve Quality of Life in Cognitive Communication Impairments, 2025

....Roles of stress, sleep hygiene, and nutrition were introduced to address a holistic approach. Intervention was personalized based on pretreatment testing, a cognitive questionnaire, and an algorithm highlighting participant-selected concerns, which ensures person-centered care. Established criteria determined when to advance skills or cognitive complexity while aiming to reduce postexertional malaise/postexercise symptom exacerbation. Examples of specific cognitive communication targets include memory strategy development, attention retraining, and expressive/receptive communication tools. A protocolized approach allows for replication of an intervention that prioritizes effort and fatigue in conjunction with traditional speech therapy.

...All participants reported a positive impact on quality of life at their final evaluation and on their 90-day survey.

Conclusions​

Speech therapy is an integral part of PASC treatment. The findings support the broader implementation of this speech therapy approach in PASC treatment.

There seems to be faith there that there will be positive progress in response to the intervention e.g. 'established criteria determined when to advance skills or cognitive complexity while aiming to reduce postexertional malaise/ post exercise symptom exacerbation'. I doubt that that faith is warranted. I don't think gradually doing more cognitive tasks increases the capacity of a person with ME/CFS to do more cognitive tasks.

I guess whether you can train your way out of the cognitive issues of ME/CFS is a reasonable question to ask, but it needs to be measured with more than a survey at the end asking people if the course helped their quality of life.

The 2025 paper did conduct baseline testing, but it does not report on the results of any post-intervention testing in the abstract. The main outcome seems to be that survey asking participants how they feel about the course. I'd like to think that the authors' recognition of the issue with subjective outcomes is what has prompted the call in their latest paper for 'multiple biological outcomes' to be assessed. But, the therapy targets in the 2025 paper of 'attention retraining' and 'expressive/receptive communication tools' raise some red flags.

It would be interesting to hear from any person with ME/CFS who has been engaging with this team.

@Peter T, you might have some insights.

 

[Peter T]

@Peter T, you might have some insights.

I will have to try to get someone to access the full paper for me. Unfortunately I am now decades out of date in terms of Speech and Language Therapy related research.

I can see a role for helping people understand the specific nature of the communication aspects impacted, which may in turn help individuals adapt their communication strategies or at least help them understand why things might be going wrong rather than just be trapped in a vague sense that everything is falling apart.

Though this approach, at least as reported in the abstract, focuses in part on developing coping strategies, that is symptom management, it seems also to involve the unevaluated rehabilitation principle of establishing what an individual can do and break down activities so they can practice those activities at or near their current ceiling level in the belief that this will result in improvement in the underlying impairment. Speech and Language Therapy (SALT) was, and I assume still is, very much trapped in the rehabilitation bubble, failing to parse the different aspects of their interventions.

If you have a nice well intentioned clinician that genuinely believes they can help you, which is likely the case, who also has provided you with some insight into what is going wrong, that has reassured you that there is not a total system failure, it is virtually inevitable that you will report a positive outcome, even if in reality there has been no change in the underlying processes. When I was still working, back in the last century, I found it frustratingly difficult to elicit critical feedback back from patients on new interventions.

Though there may be a roll for SALT in researching the impacts of Long Covid and preparing information/materials for people with Long Covid, I suspect those needing direct intervention from a SALT to be very much in the minority, and that such clinicians’ involvement though potentially providing coping strategies is unlikely to impact any underlying deficits.

[edited to correct some typos and add the following - Does this SALT in Long Covid paper require its own thread?

(I still am pondering a thread to discuss the different components of what is ‘rehabilitation’ and are there components of ‘rehabilitation’ in the sense of what rehabilitation professionals do in a clinical setting that may have a value regardless of the often misguided and generally doomed attempt to magically restore underlying processes through targeted practice in an unreal clinical setting?)]

 

[lelelemonade]

I dislike the term “emotional exertion”. I think it stretches the definition of “exertion”. I also kinda disagree that emotions can cause PEM, though my argument may be pedantic. I think it’s not the emotion itself but the excitement that accompanies it. Being in a state of heightened alertness for any reason often leads to PEM in my experience. I’m not sure if being in that state alone is enough to trigger it, because it usually prompts me to engage in mental activity too. It can be accompanied by fear, anger, enthusiasm, or no discernible emotion at all. At the same time, intense sadness and joy rarely lead to PEM. I can cry and laugh pretty much all I want as long as don’t exhaust myself physically or by talking to people. That was my experience when I was moderate, and it remains true now that I’m very severe.

 

[Verity]

I agree with @lelelemonade. The only emotions that provoke PEM for me are ones that come with physical tension, increased heart rate, etc. Usually this is anger or anxiety.

 

[Jonathan Edwards]

I dislike the term “emotional exertion”.

Yes, I think narcolepsy shows how little insight we have into how we should classify these mental triggers. In nercolepsy you only go paralysed if you are pleasantly surprised. Goodness knows how that relates to 'exertion'.

 

[Hoopoe]

I dislike the term “emotional exertion”. I think it stretches the definition of “exertion”. I also kinda disagree that emotions can cause PEM, though my argument may be pedantic. I think it’s not the emotion itself but the excitement that accompanies it. Being in a state of heightened alertness for any reason often leads to PEM in my experience. I’m not sure if being in that state alone is enough to trigger it, because it usually prompts me to engage in mental activity too. It can be accompanied by fear, anger, enthusiasm, or no discernible emotion at all. At the same time, intense sadness and joy rarely lead to PEM. I can cry and laugh pretty much all I want as long as don’t exhaust myself physically or by talking to people. That was my experience when I was moderate, and it remains true now that I’m very severe.

I agree. To me, emotional exertion sounds like doing emotional labour. Like working through some conflicts, processing relationship issues, dealing with traumatic experiences.

Other people could misinterpret it as a statement about draining negative emotions and thoughts are, when positive emotions can also be very draining for those with ME/CFS. What is meant is precisely the state of heightened brain activity, which happens to often be associated with emotions.

A state of positive emotion may be more exhausting than a negative one because it is more difficult to resist good feelings, so we want to continue exposing ourselves to the situation/activity that is triggering them, and the positive feelings can suppress the warning signals.

 

[Hutan]

While emotional and cognitive exertion are documented as contributing factors to PEM, activities eliciting these forms of exertion in addition to or instead of physical effort are rarely included.

I suppose the abstract/poster may be noting that lots of resources on PEM suggest that emotional and cognitive exertion can bring on PEM, and actually, those ideas have not been well tested. Which is true, and probably worth highlighting.

It's just hard to know what motivated this effort, and where it might go next, especially with the limited affiliation information. Hence my look at what the first author had done before and slight concern about the promotion of a programme that seemed to have an element of cognitive 'pacing-up'.

 

[rvallee]

This could have potential value, but nothing I have seen out of how mental health research works, or medicine in general, suggests this is feasible. I'm sure they can cook up something that might superficially seem relevant, but will entirely miss the mark in just the way that it serves no purpose but ends up being harmful.

This is subjective interpretation about subjective perception of emotions. Even without the "of emotions" part this is simply not something where medicine has achieved relevant skills or tools. I have no idea what they think they can achieve here, I would frankly expect more out of a bunch of medieval peasants trying to fix a modern car engine.

 

[MrMagoo]

I dislike the term “emotional exertion”. I think it stretches the definition of “exertion”. I also kinda disagree that emotions can cause PEM, though my argument may be pedantic. I think it’s not the emotion itself but the excitement that accompanies it. Being in a state of heightened alertness for any reason often leads to PEM in my experience. I’m not sure if being in that state alone is enough to trigger it, because it usually prompts me to engage in mental activity too. It can be accompanied by fear, anger, enthusiasm, or no discernible emotion at all. At the same time, intense sadness and joy rarely lead to PEM. I can cry and laugh pretty much all I want as long as don’t exhaust myself physically or by talking to people. That was my experience when I was moderate, and it remains true now that I’m very severe.

Yes that’s interesting, I had a period of complex grief and it didn’t cause PEM despite not eating/sleeping frequently crying and being half-mad for most of a year.

 

[NelliePledge]

I agree that positive or negative emotions in themselves don’t result in PEM but the situation in which these emotions are being experienced. Generally that will be some type of social interaction, involving both physical and social exertion. I’ve been really exhausted after watching my football team win. I couldn’t understand it as it had been such fun. But then I realised there had been three goals. If it is a good game and lots of goals/attempts on goal I am up on my feet a lot more and cheering, more chatter during and after the match. If I was watching that at home on tv I would still be just as happy, cheering, but there would be 10% of the physical exertion and I wouldn’t be talking to anyone but myself.

The emotional aspect is a distraction that makes it more likely I will go over physical and cognitive capacity. Same goes for upsetting events like funerals.