Autonomic dysfunction and exercise intolerance in post-COVID-19 - An as yet underestimated organ system?

Individuals recovering from COVID-19 often present with persistent symptoms, particularly exercise intolerance and low cardiorespiratory fitness. Put simply, the Wasserman gear system describes the interdependence of heart, lungs, and musculature as determinants of cardiorespiratory fitness. Based on this system, recent findings indicate a contribution of peripheral, cardiovascular, and lung diffusion limitations to persistent symptoms of exercise intolerance and low cardiorespiratory fitness. The autonomic nervous system as an organ system involved in the pathophysiology of exercise intolerance and low cardiorespiratory fitness, has received only little attention as of yet. Hence, our article discusses contribution of the autonomic nervous system through four potential pathways, namely alterations in (1) cerebral hemodynamics, (2) afferent and efferent signaling, (3) central hypersensitivity, and (4) appraisal and engagement in physical activity. These pathways are summarized in a psycho-pathophysiological model. Consequently, this article encourages a shift in perspective by examining the state of the pulmonary and cardiovascular system, the periphery, and auxiliary, the autonomic nervous system as potential underlying mechanisms for exercise intolerance and low cardiorespiratory fitness in patients with post-COVID-19.