IMAGE DESCRIPTION: An image of a human body showing the muscles in the shoulder and upper arm with a circular image showing a man having a Cardiopulmonary Exercise Test (CPET). Title reads: Science Norway: Why does physical activity exacerbate symptoms in ME/CFS and Long Covid patients? The ME Association Logo (bottom right)

Science Norway: Why does physical activity exacerbate symptoms in ME/CFS and Long Covid patients?

Researchers can argue about a lot. But in one area, researchers worldwide have been remarkably unanimous: Physical activity is healthy for both body and mind.

But for ME/CFS sufferers, and some patients with other illnesses like Long Covid and fibromyalgia, this is often not the case. Instead, fairly mundane activities can send them to bed for days, with symptoms like extreme fatigue, flu-like feelings, pain, brain fog, and – paradoxically – sleep problems. This is called PEM – post-exertional malaise.

By Ingrid Spilde


But what is post-exertional malaise (PEM)?

  • Exercise-induced worsening of symptoms is a characteristic feature of ME/CFS. It has also been reported among some Long Covid patients and people with Fibromyalgia.
  • The phenomenon is often referred to as PEM (post-exertional malaise). Some also call it PESE (post-exertional symptom exacerbation) or PENE (post-exertional neuroimmune exhaustion).
  • PEM involves a worsening of symptoms after physical, mental, or emotional exertion that would not have caused problems before the illness.
  • PEM can be triggered by cognitive, physical, emotional, or social activity.
  • PEM can cause a wide range of symptoms. The most common are extreme fatigue, feeling like you have the flu, body aches, sleep disturbances, and cognitive problems like brain fog.
  • The symptoms are often delayed and are typically worst 12 to 48 hours after the activity. They can last for days or even weeks. In the worst case, PEM can lead to long-term worsening of the illness.

Testing exercise capacity

A type of test called repeated CPET (Cardiopulmonary Exercise Test) measurements can precisely show how a session of physical activity affects a person’s condition afterwards. Researchers then get a picture of what happens in the body while the person is exercising.

Characteristic differences

Such studies, including a Norwegian study from 2019, have shown characteristic differences between ME/CFS patients and healthy individuals.

A summary from 2022 concludes that ME/CFS patients are in significantly worse condition on the second test. They perform worse and the lactic acid in their muscles builds up faster. This does not happen with healthy people.

It also does not happen with people who have other serious chronic diseases such as heart failure, COPD, and cystic fibrosis.

They believe the research suggests that ME/CFS patients may have changes in energy metabolism in their muscles and the response of the autonomic nervous system. This is the part of the nervous system that controls heart rate, blood pressure, breathing, and digestion.

Problems in the cells' powerhouses

Rob Wüst from the Vrije Universiteit Amsterdam and his colleagues had taken muscle samples from healthy individuals and those with long Covid, both before and after a controlled 15-minute exercise session.

It turned out that long Covid patients stood out even before the test. Their muscles had a greater proportion of fast-twitch muscle fibres. And after exercise, even more differences emerged. There were signs of severe muscle damage and lower activity in the mitochondria, which are the cells' powerhouses.

The researchers also observed that long Covid patients had muscles that were less able to absorb oxygen from the blood than healthy individuals.

The study had relatively few participants, and more research is needed before it can be confirmed that these changes are characteristic in those with PEM. But the results also suggested interesting areas that could be investigated further.

Not a result of poor fitness

In a summary from 2023, Systrom and his colleagues write that poor fitness does not lead to the physical changes that they see in the bodies of ME/CFS and Long Covid patients with PEM.

Sommerfelt suggests that the illness' progression often indicates that PEM is not related to poor fitness due to long-term inactivity.

PEM occurs at the onset of the illness. Most people can remember which week they fell ill, and PEM is a characteristic already from the first weeks and months.

Kristian Sommerfelt is a paediatrician and senior physician at the Østfold Hospital Trust Kalnes and professor emeritus at the University of Bergen

We don’t primarily need studies of the effect of individual measures, but investigations to gain a more fundamental understanding of what PEM is.

Nina Køpke Vøllestad is a professor at the University of Oslo.

Read more

ME Association Blog: The Guardian: Long Covid and Mitochondrial Dysfunction  |  January 2024

Shopping Basket