Autonomic Dysfunction and Low Cardio-Respiratory Fitness in Long-Term Post-COVID-19 Syndrome

<b>Purpose:</b> Post-COVID-19 syndrome (PCS) is characterized by low cardio-respiratory fitness (CRF). Recent research focuses on the role of autonomic nervous system dysfunction (AD) as a potential contributor to the diminished exercise performance. The aim is to determine the prevalence of AD-chronotropic insufficiency (CI) and abnormal heart rate recovery (HRR) in long-term PCS subjects and to analyse their association with exercise capacity. <b>Patients and Methods:</b> A total of 192 subjects with a history of SARS-CoV-2 infection were included. Chronic Fatigue Syndrome Questionnaire (CFSQ) was applied, and two symptomatic and asymptomatic emerged. Forty-seven had post-COVID complaints, persisting up to thirty months post-acute episode. CI and HRR were determined during the cardio-pulmonary exercise test (CPET). <b>Results:</b> Symptomatic subjects were divided into mild (20) and moderate-severe (27), depending on the CFSQ score; forty-eight PCS subjects without complaints served as a control group. Subjects with moderate-severe PCS showed lower peak VO2 (24.13 ± 6.1 mL/min/kg vs. 26.73 ± 5.9 mL/min/kg, vs. 27.01 ± 6.3 mL/min/kg), as compared to the mild/asymptomatic subjects. Diminished physical activity was established in 10 (37%) of the moderate-severe, 7 (35%) of the mildly symptomatic and 14 (29%) of the asymptomatic groups. The occurrence of AD in the mild/moderate-severe and control groups were, respectively, CI 35% vs. 81.5% vs. 12.5%. Abnormal HRR was, respectively, 20% vs. 33% vs. 8%. None of the subjects had depleted breathing reserve, dynamic hyperinflation, exercise bronchospasm or desaturation. Neither CI nor abnormal HRR correlated to peak O2. <b>Conclusions:</b> AD is present among long-term PCS subjects and may limit the cardio-respiratory response to exercise but is not independently associated with it. Assuming the multiorgan ANS innervation, it is highly probable that AD has diverse pathological pathways in the various PCS phenotypes and contributes differently by cerebral, cardiovascular, respiratory, peripheral or mixed pathways to the diminished neuro-cognitive and physical performance.