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29/07/2025 - Institutional news

One of the Possible Causes of Chronic Fatigue in People with Long COVID Identified

A study by the Pneumology, Pathology, and Intensive Care Services at Hospital del Mar suggests that fatigue in long COVID patients may be related to fibrosis caused by the infection in the walls of blood vessels. This would hinder the delivery of oxygen to muscle fibers and limit the capacity for prolonged exercise. At the same time, it opens the door to the possibility of recovery.

One of the symptoms associated with long COVID is chronic fatigue. Until now, its origin was unclear. A study conducted by the Pneumology, Pathology, and Intensive Care Services at Hospital del Mar, along with researchers from the Hospital del Mar Research Institute, points to a potential cause: fibrosis in the walls of blood vessels triggered by the infection. The study has been published in the journal Ultrastructural Pathology.

The research is based on muscle biopsies taken from the quadriceps of 35 patients admitted to Hospital del Mar during the pandemic. Eight of these samples were analyzed using electron microscopy to assess the state of the tissue. Significant fibrosis was found in the walls of the capillaries supplying blood to the muscle fibers, a finding consistent with observations in other organs from patients who died from COVID-19.

From left to right: Joaquim Gea, Josep Lloreta, Sergi Pascual and Joan Ramon Masclans

The COVID-19 virus infection destroys the endothelial cells that form the walls of blood vessels. The body's response causes thickening of these walls, making gas exchange more difficult in the capillaries that deliver oxygen to muscle cells. "If there is a problem with this gas exchange mechanism between capillaries and muscle fibers, you can still perform short muscular activities, but not prolonged ones - you get fatigued more easily", explains Dr. Joaquim Gea, Emeritus Head of the Pneumology Service and researcher at the Hospital del Mar Research Institute. This mechanism could explain the chronic fatigue experienced by people with long COVID.

"This situation is also seen in other organs, such as in pulmonary fibrosis or in post-intensive care syndrome (PICS), which results in significant functional limitations in patients who have undergone a critical episode in an Intensive Care Unit. It may open up a new area of study to identify even preventive treatments", adds Dr. Joan Ramon Masclans, Head of the Intensive Care Service at Hospital del Mar and coordinator of the Critical Illness Research Group at the institute.

The results of this study may support the use of muscle biopsy as a diagnostic tool in people with long COVID and chronic fatigue. As pathologist Dr. Josep Lloreta, who conducted the analysis, explains, "Electron microscopy allows for a very detailed analysis of the subtle changes caused by diseases".

At the same time, this research opens the door to the possibility of treatment to compensate for the reduced ability of these capillaries to deliver oxygen to the muscles through aerobic exercise training. "This type of exercise can promote the formation of new capillaries capable of efficiently transporting oxygen. These individuals could improve if they engage in aerobic exercise", says Dr. Gea.

Reference Article
Lloreta-Trull J, Marin-Corral J, Juanpere N, Pascual-Guardia S, Gimeno J, Naranjo D, Segalés L, Hernández S, Simón M, Serrano L, Casado B, Lloveras B, Gea J. Muscle disease in severe COVID-19 patients: a microangiopathic myopathy. Ultrastruct Pathol. 2025;49(3):296-305. doi: 10.1080/01913123.2025.2488809. Epub 2025 Apr 21. PMID: 40257175.

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