Microclots and Exercise Intolerance in Long COVID: The Biology Behind Why Exercise Can Make Symptoms Worse

Updated October 2026 | Long Covid Journey | Research explained for patients

Why Does Exercise Make Long COVID Worse? The Science Behind Microclots and Exercise Intolerance

Exercise can make Long COVID symptoms worse because the body may struggle to deliver oxygen, produce energy and recover normally after exertion. Research has identified abnormalities in muscles, mitochondria, blood-vessel function and inflammation. Scientists are also investigating whether tiny fibrin-rich particles, known as microclots, contribute to these problems.

Think about walking up a flight of stairs. Before COVID, your muscles received the oxygen and energy they needed, and you recovered within minutes. With Long COVID, that same activity may leave your legs unusually heavy, your heart racing or your body exhausted. Some people experience an even more dramatic reaction: hours later, or the following day, their symptoms worsen and they may struggle to get out of bed. This is known as post-exertional malaise (PEM).Research led by Rob Wüst and colleagues in Amsterdam has found measurable muscle abnormalities and disturbances in energy metabolism in people with Long COVID who experience PEM. Other researchers have reported changes in microclot populations and inflammatory markers following exercise.The important discovery is that exercise intolerance in Long COVID is not necessarily a simple fitness problem.Researchers are finding biological changes that may help explain why activities that once felt effortless can now leave people unwell. Microclots are one possible part of this explanation, alongside muscle, metabolic and vascular abnormalities.

5 Key Facts About Microclots and Exercise Intolerance in Long COVID

1. Long COVID exercise intolerance is not always caused by being unfit. Research has identified measurable abnormalities in muscles, oxygen use and energy metabolism. This may help explain why someone who previously walked for miles now struggles with a short trip to the supermarket.
2. Rob Wüst’s Amsterdam research found biological changes linked to post-exertional malaise (PEM). Muscle biopsies revealed abnormalities in muscle structure and metabolism, with worsening muscle pathology after exercise. These findings help explain why exertion can have consequences beyond ordinary tiredness.
3. Microclots may be part of the oxygen-delivery problem. Researchers have identified unusual fibrin-rich particles in samples from some people with Long COVID. Scientists are investigating whether these particles, together with inflammation and blood-vessel dysfunction, interfere with the circulation that supplies muscles and organs.
4. Exercise may trigger measurable changes in the blood. Research involving repeated exercise tests reported changes in microclot populations, inflammatory markers and exercise performance. This raises the possibility that exertion affects biological processes involved in symptom worsening, although the precise cause-and-effect relationship is still being studied.
5. Pushing through Long COVID symptoms can make some people worse, particularly those with PEM. A short walk, household chores or even a demanding conversation may be followed by a crash lasting days. Understanding individual limits and avoiding repeated symptom exacerbation is important; recovery cannot simply be measured by how much exercise someone manages.

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When Ordinary Movement Becomes Extraordinary Effort

Imagine waking up and deciding to do something completely ordinary: walk to the local shop, take a shower or change the bedsheets. Before COVID, you probably wouldn’t have considered any of these activities exercise. Now you might have to choose between them.

You manage the walk, but halfway home your legs begin to feel strangely heavy. Your heart is beating faster than it should. You stop to catch your breath, wondering how something so simple has become so difficult. Or perhaps you feel fine while doing it, only for the real consequences to arrive later. That evening, your muscles ache and your head feels foggy. The following morning, even making breakfast seems overwhelming.

How can such a small amount of activity cause such a big reaction?

For years, people living with Long COVID have asked this question. Many were told they were deconditioned, anxious about exercise or simply needed to rebuild their fitness. But researchers have started looking much deeper. In Amsterdam, Rob Wüst and colleagues examined muscle tissue from people with Long COVID and found abnormalities in muscle structure and energy metabolism, including changes associated with post-exertional malaise. Other scientists are studying the blood itself, investigating unusual fibrin-rich particles called microclots, inflammation and problems involving the smallest blood vessels.

Why does this matter? Because your muscles need two things to work properly: a reliable supply of oxygen and the ability to turn that oxygen and fuel into usable energy.

Imagine a city where deliveries are arriving late and the factories are struggling to operate efficiently. Even if the city looks normal from the outside, everyday work becomes harder. Something similar may be happening in parts of the body affected by Long COVID. The blood vessels deliver oxygen and nutrients, while muscle cells use them to produce energy. If either process is disrupted, even ordinary movement can become unexpectedly demanding.

This does not mean researchers have found one explanation for everyone. Microclots, vascular dysfunction, mitochondrial abnormalities and inflammation may play different roles in different people. But the growing evidence is helping explain something patients have been saying for years: the problem is not necessarily that we have forgotten how to exercise. It may be that our bodies are no longer responding to exercise in the way they once did.

And that changes the questions we should be asking. Instead of simply asking how to increase activity, we need to understand why activity causes symptoms, what happens inside the body during exertion and how recovery can be supported without repeatedly making people worse.

In this article, we explore what scientists are discovering about microclots, blood vessels, muscles and oxygen delivery—and why this research matters to people living with Long COVID.

For practical guidance on movement and PEM, read our Can You Exercise With Long COVID and PEM? A Guide to Safe Movement.

That question deserves serious investigation.

What Are Microclots, and Why Do They Matter in Long COVID?

Think of your blood vessels as a delivery network. Their job is to carry oxygen and nutrients to your muscles, brain and organs. The smallest vessels, called capillaries, are where much of that exchange happens. If this system struggles, even simple activities can become exhausting.

Researchers have identified unusual fibrin-rich particles, known as microclots, in blood samples from some people with Long COVID. Unlike the larger clots associated with thrombosis, these microscopic structures are being investigated for their possible effects on circulation, inflammation and oxygen delivery. Scientists are exploring whether microclots, together with damage or dysfunction in the blood-vessel lining (endothelium), could help explain symptoms such as fatigue, breathlessness and exercise intolerance.

The important question is whether these particles contribute to impaired blood flow and symptoms, rather than simply being a sign of another underlying process. Their presence has been observed; their precise role in Long COVID is still being established.

Why Can Exercise Make Long COVID Symptoms Worse?

Normally, exercise increases the body’s demand for oxygen and energy. Your heart pumps faster, your muscles work harder and, with adequate recovery, your body adapts. But for some people with Long COVID, even walking to the shops or climbing stairs can trigger breathlessness, heavy legs, a racing heart or profound exhaustion. Others feel reasonably well during the activity but experience a significant worsening of symptoms hours later or the following day.

Researchers are investigating several possible explanations, including impaired oxygen delivery, abnormalities in muscle energy production, inflammation and changes in the smallest blood vessels. These findings help explain why exercise intolerance in Long COVID is not necessarily the same as ordinary deconditioning, and why simply pushing harder may worsen symptoms in people who experience post-exertional malaise (PEM).

What Did Rob Wüst’s Amsterdam Research Discover?

Research led by Rob Wüst and colleagues in Amsterdam has provided important biological evidence of why exercise can be so difficult for people with Long COVID. In a 2024 Nature Communications study, researchers compared 25 patients experiencing PEM with 21 people who had recovered from COVID. By examining muscle biopsies before and after exercise, they identified reduced exercise capacity, abnormalities in muscle structure and metabolism, and worsening muscle pathology following exertion.

The findings matter because they show that something measurable is happening inside the muscles. Mitochondria, the structures responsible for producing much of the energy cells use, are part of this picture. If muscles cannot produce or use energy efficiently, activities that once felt effortless may become disproportionately demanding.

Further research published in Nature Communications in 2026 found that muscle abnormalities in Long COVID and ME/CFS differ from changes caused by bed rest. This is particularly significant for patients who have been told their symptoms are simply the result of inactivity. Deconditioning may contribute to reduced fitness, but it does not adequately explain all the biological changes researchers are finding.

What Happens to Microclots During Exercise?

A separate study involving researchers at the University of Derby examined 46 people with Long COVID who completed two submaximal exercise tests approximately 24 hours apart. Researchers found that after exertion, larger microclot populations decreased while smaller particles increased, alongside changes in inflammatory and vascular-injury-associated markers. Participants also showed reduced measures of exercise performance on the second day.

The researchers interpreted these findings as consistent with microclot fragmentation during exercise. In simple terms, instead of disappearing, some larger fibrin-rich particles appeared to break into smaller ones. This raises an important possibility: could exertion change the blood and inflammatory environment in ways that contribute to worsening symptoms?

The study was released as a preprint, and participants at high risk of PEM were excluded. It therefore cannot establish that fragmented microclots directly damage capillaries or cause PEM. Nevertheless, the findings add another biological dimension to exercise intolerance research.

Taken together, the Amsterdam muscle studies and the microclot research are helping explain why Long COVID can change the body’s response to exertion. The problem may involve not just how much oxygen reaches the muscles, but how effectively those muscles use it and how the body responds afterwards. For someone who can no longer manage a short walk without becoming unwell, that distinction matters. It shifts the conversation from simply rebuilding fitness to understanding what is happening inside the body.

The Oxygen Problem: Why Normal Oxygen Levels Don’t Tell the Whole Story

Your pulse oximeter might show 98% oxygen, yet walking upstairs leaves you breathless and exhausted. How is that possible? Because having oxygen in your blood is not the same as delivering and using it efficiently in your muscles.

Researchers are investigating whether Long COVID affects the smallest blood vessels (microvascular dysfunction), their inner lining (endothelial dysfunction) and the mitochondria that help cells produce energy. Autonomic dysfunction may also disrupt heart rate and blood-flow regulation, while inflammation can affect how muscles respond to exertion.

These processes may overlap, helping explain why one person becomes breathless after a short walk, another experiences painful, heavy legs, and someone else feels reasonably well until a severe crash arrives the following day. A normal oxygen reading does not rule out problems with exercise physiology, although persistent or worsening breathlessness still deserves medical assessment.

Exercise Intolerance vs PEM: What’s the Difference?

Exercise intolerance means struggling to perform an activity that previously felt easy. You might become breathless, weak or dizzy simply walking to the shops. Post-exertional malaise (PEM) is different: it is a disproportionate worsening of symptoms after physical, mental or emotional effort, sometimes delayed by hours or until the following day. A crash can bring profound fatigue, muscle pain, brain fog, flu-like symptoms and a recovery period lasting days or longer.

The two frequently overlap. Amsterdam researchers have identified muscle abnormalities associated with PEM, while the Derby study found changes in microclot populations and inflammatory markers after exercise in patients selected to have a lower risk of PEM. These findings suggest different biological processes may contribute to symptom worsening, although researchers have not established that PEM and exercise intolerance have entirely separate causes.

Why a Short Walk Can Feel Like a Marathon

Before Long COVID, walking to the supermarket might have taken ten minutes. Now you may need to calculate whether you can stand in the queue, carry your shopping home and still have enough energy to prepare dinner. Sometimes the hardest part isn’t the walk itself, but not knowing how much it will cost you tomorrow.

When muscles struggle to meet their energy demands, everyday activities can become disproportionately difficult. If PEM is present, the consequences may continue long after the activity ends. This is why Long COVID cannot always be approached like ordinary deconditioning: someone rebuilding fitness may feel tired after exercise, while someone experiencing PEM may become significantly more unwell. The difference matters when deciding how to manage activity and recovery.

What Does This Mean for Exercise and Rehabilitation?

More exercise is not automatically better for everyone with Long COVID. Some people benefit from carefully tailored rehabilitation, while others, particularly those with PEM, experience worsening symptoms when activity is increased too quickly or beyond their limits.

Pacing means understanding how much physical, cognitive and social activity your body can tolerate without repeatedly triggering symptom crashes. It is not a treatment proven to remove microclots or repair blood vessels, but it can help people manage PEM. Rehabilitation should reflect individual symptoms and medical needs rather than follow a fixed programme of increasing exercise regardless of the consequences.

For practical guidance, read Can You Exercise With Long COVID and PEM? A Guide to Safe Movement.

Could Treating Microclots Improve Exercise Intolerance?

If microclots contribute to impaired circulation, could removing them help restore exercise capacity? This is one of the questions researchers are investigating. Potential approaches include anticoagulants, antiplatelet medications and treatments targeting clot breakdown or vascular inflammation.

The challenge is determining whether microclots are contributing directly to symptoms, which patients might benefit from treatment and whether the potential improvements outweigh the risks. No anticoagulant or antiplatelet treatment has yet been established as an effective therapy for Long COVID-related microclots. These medications can cause serious bleeding and should not be started solely because someone has Long COVID or suspected microclots.

Explore the research in Enoxaparin in Long COVID: Anticoagulation, Microclots and Vascular Dysfunction.

Why Research Into Exercise Intolerance Matters

Not everyone with Long COVID experiences the same symptoms. Some struggle mainly with breathlessness, others with muscle weakness, dysautonomia or PEM. Some gradually regain their exercise capacity, while others remain severely limited. This variation may reflect different combinations of vascular, muscular, metabolic and immune abnormalities.

What makes the research from Amsterdam, Derby and other centres important is that scientists are identifying measurable biological changes that help explain why exertion can become so difficult. Muscle abnormalities, altered energy metabolism, inflammation and microclot-related changes are offering new ways to investigate experiences patients have described for years.

For someone who once ran five kilometres but now struggles to climb a flight of stairs, this research offers something meaningful: a better understanding of why the body may no longer respond normally to effort. The next challenge is translating those discoveries into reliable tests, safer rehabilitation and treatments that genuinely improve patients’ lives.

Long COVID exercise intolerance is not simply about how much activity someone can manage. It is about understanding why their body responds differently and what might help it recover.

Frequently asked questions

A Note From Long Covid Journey

Long Covid Journey is a patient-led information resource.

We believe that people living with Long COVID deserve access to emerging scientific research without having to navigate complicated medical papers or misleading treatment promises.

Research into microclots, muscle abnormalities and exercise intolerance is evolving. We aim to explain what studies have found, why the findings matter and where important uncertainties remain.

Our lived experience helps us ask the questions. The evidence determines how we answer them.

Medical disclaimer: This article is for education and information only and does not replace individual medical advice. Exercise intolerance and breathlessness can have several causes, some requiring investigation or urgent treatment. Seek prompt medical attention for new or severe chest pain, fainting, significant breathlessness or other concerning symptoms. Do not begin anticoagulant or antiplatelet treatment without appropriate medical supervision.

Related Reading: Microclots, Blood Vessels and Long COVID

1. Could Tiny Blood Vessel Problems Be Driving Long COVID? — Explore the research into microclots, endothelial dysfunction and impaired microcirculation.
2. Long COVID and Blood Vessels: The Hidden Role of Vascular Dysfunction — Understand how blood-vessel abnormalities may affect oxygen delivery, fatigue and exercise intolerance.
3. Why Does Capillary Health Matter in Long COVID Recovery? — Discover why the body’s smallest blood vessels matter and what researchers are finding about oxygen extraction.
4. Endothelium Damage in Long COVID: What It Means for Your Symptoms — Learn how dysfunction of the blood-vessel lining may contribute to symptoms across different organs.
5. Enoxaparin in Long COVID: Anticoagulation, Microclots and Vascular Dysfunction — Examine the research behind anticoagulants, possible benefits and important treatment risks.
6. Long COVID Treatments: What Actually Works? — Compare the evidence for treatments targeting blood flow, vascular dysfunction, clotting and other Long COVID mechanisms.
7. Microclots and Exercise Intolerance in Long COVID: Why Exercise Can Make Symptoms Worse — Explore emerging research into microclot changes, muscle abnormalities and exercise-related symptom worsening.

Scientific References: Microclots, Vascular Dysfunction and Exercise Intolerance

1. Circulating Microclots Are Structurally Associated With Neutrophil Extracellular Traps and Their Amounts Are Elevated in Long COVID Patients — Thierry et al., Journal of Medical Virology, 2025. Investigates the relationship between fibrin-rich microclots and neutrophil extracellular traps (NETs), suggesting a possible connection between inflammation and abnormal clotting.
2. Muscle Abnormalities Worsen After Post-Exertional Malaise in Long COVID — Appelman et al., Nature Communications, 2024. Research involving Rob Wüst’s Amsterdam team identifying skeletal muscle abnormalities and metabolic disturbances associated with PEM.
3. Persistent Exertional Intolerance After COVID-19: Insights From Invasive Cardiopulmonary Exercise Testing — Singh et al., CHEST, 2022. Demonstrates impaired peripheral oxygen extraction during exercise in a small group of patients with persistent post-COVID exercise intolerance.
4. Exercise-Induced Changes in Microclotting and Cytokine Levels Point to Vascular Injury and Inflammation in People With Long COVID — Thomas et al., 2025 preprint. Explores changes in microclot populations, inflammatory markers and exercise performance following repeated exertion. Findings remain preliminary.
5. Persistent Endothelial Dysfunction Is Associated With Exercise Intolerance in Adults Despite Preserved Myocardial Work Three Years After SARS-CoV-2 Infection — 2026. A small case-control study reporting impaired blood-vessel function associated with reduced exercise capacity, despite preserved measures of cardiac work.
6. Skeletal Muscle Properties in Long COVID and ME/CFS Differ From Those Induced by Bed Rest — Nature Communications, 2026. Investigates how muscle abnormalities in Long COVID and ME/CFS differ from changes caused by inactivity alone.
7. Exercise Intolerance in Post-Acute Sequelae of COVID-19 and the Value of Cardiopulmonary Exercise Testing — Frontiers in Medicine, 2022. Reviews the evidence for reduced exercise capacity, impaired peripheral oxygen extraction and other physiological abnormalities following COVID-19.