Long-COVID syndrome: pathophysiology of the impaired exercise tolerance

Finanziato da MUR

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A substantial percentage of patients recovering from the SARS-CoV-2 infection present, weeks/months after hospital discharge, a constellation of persistent symptoms that significantly affect their health status, capacity to resume work or leisure activities, quality of life and compliance to rehabilitation interventions, leading to a vicious circle characterized by exercise intolerance – inactivity – worsened exercise intolerance. This condition (“long-COVID 19 syndrome”), and its landmark symptoms of excessive fatigue, exercise intolerance, dyspnea, muscle pain etc., would need to be interrupted/reversed by effective interventions, since they negatively affect the patients’ quality of life and represent a significant burden for the public health system. However, any preventive/therapeutic/rehabilitation intervention aimed at improving exercise tolerance needs to be based on a precise knowledge of the patho-physiological mechanisms responsible for the signs/symptoms. This knowledge is substantially lacking for the long-COVID 19 syndrome patients. Oxidative metabolism, the metabolic process which allows ATP resynthesis through the oxidation of substrates, is responsible for substantially all the energy yield for muscular activities lasting longer than 1-2 minutes. Potential mechanisms, along the pathway for O2 from ambient air to skeletal muscles mitochondria, which could be responsible for the impaired exercise tolerance in patients with the long-COVID syndrome, include respiratory factors (“wasted ventilation”, respiratory inefficiency), cardiovascular factors, microvascular/endothelial factors, sarcopenia, the impairment of skeletal muscle oxidative metabolism and of mitochondrial respiration. The present project aims to identify the patho-physiological mechanisms responsible for exercise intolerance in long-COVID patients and biomarkers quantifying the impairment at the different levels mentioned above. A translational approach will be followed to this aim, bringing methods and approaches developed over the years in the exercise physiology laboratories to the “bed of the patient”. Specific and personalized exercise training interventions will also be implemented in the last stages of the project.



  • Università degli Studi di Verona
  • Università degli Studi di Udine


Importo del progetto

Importo totale del progetto        Euro 114.963,00
Importo del progetto Uniud        Euro 93.874,00
Finanziamento Uniud                Euro 21.089,00



  • Dal 18/10/2023
  • Al 17/10/2025