Mechanisms underlying exercise intolerance in long COVID: An accumulation of multisystem dysfunction

Area of Science:

• Physiology
• Pathology
• Exercise Science

Background:

• Long COVID, following SARS-CoV-2 infection, presents with unexplained exercise intolerance and fatigue.
• The underlying mechanisms of these symptoms are not fully understood.
• Understanding these mechanisms is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the physiological basis of exercise intolerance in long COVID.
• To compare exercise performance, cardiopulmonary function, vascular health, skeletal muscle oxidative capacity, and autonomic nervous system function between long COVID patients and healthy controls.
• To identify potential contributing factors to impaired exercise tolerance in long COVID.

Main Methods:

• Recruited 32 long COVID patients and 19 age-/sex-matched healthy controls.
• Assessed exercise performance, lung and cardiac function, vascular health, skeletal muscle oxidative capacity (using near-infrared spectroscopy), and autonomic nervous system function.
• Compared physiological measures between groups and against normative values, adjusting for confounders.

Main Results:

• Long COVID patients exhibited significantly reduced oxygen uptake efficiency slope and anaerobic threshold compared to healthy controls.
• Skeletal muscle oxidative capacity was lower in long COVID patients.
• Autonomic nervous system measures were abnormal in 39% of long COVID cases, falling below normal limits.

Conclusions:

• Long COVID is associated with reduced exercise performance and skeletal muscle oxidative capacity, suggesting mitochondrial pathology.
• The absence of microvascular dysfunction points towards intrinsic muscle issues.
• Autonomic nervous system dysregulation is prevalent and may contribute to impaired exercise tolerance.