Exertional Chronotropic Response and Fatigue in Individuals Post-COVID

The SARS-CoV-2 virus has a diverse physiological effect on major organ systems, affecting quality of life for many people. A mechanism that may underlie the persistent fatigue commonly reported months after the initial infection may be related to autonomic dysfunction. Evaluation of the heart rate response during exercise (i.e., chronotropic response, CR) may provide insights into the presence of autonomic dysfunction after SARS-CoV-2 infection. PURPOSE: To examine the CR in individuals post-COVID, and its relationship to self-reported levels of fatigue. METHODS: Thirty-three individuals reporting fatigue and/or physical limitations who were ≥ 4 weeks post SARS-CoV-2 infection, were enrolled in an on-going clinical trial (NCT04595773). Subjects performed an incremental treadmill cardiopulmonary exercise test (CPET), and completed the Patient-Reported Outcomes Measurement Information System-57 Profile (PROMIS-57) questionnaire for health-related quality of life. Gas exchange and heart rate were measured throughout the CPET. Peak effort was established as RER ≥1.1. Predicted VO2peak was calculated based on subject demographics. The CR was assessed by the slope of heart rate reserve (HRR) and METs throughout the CPET, and also calculated at peak exercise as [HRpeak - HRrest / APMHR - HRrest] x 100%. Chronotropic incompetence (CI) was established as <0.8. Pearson’s correlations were used to observe relationships between CR variables and the fatigue domain from PROMIS-57. RESULTS: Percent predicted VO2peak for all subjects was 100 ± 24%. Twenty-nine individuals (88%) reached peak effort on their CPET. The HRR/MET slope and the response at peak exercise was 0.91 ± 0.16 and 0.90 ± 0.15, respectively, with 4 (12%) and 6 subjects (18%) meeting criteria for CI. There were no significant relationships between self-reported fatigue and the HRR/MET slope (p = 0.10) or at peak exercise (p = 0.07). CONCLUSIONS: In this cohort of post-acute COVID-19 individuals with persistent fatigue, a subset of subjects presented with CI, and those with a blunted CR tended to report higher levels of fatigue. Autonomic dysfunction may be present in some individuals post-COVID, and future studies should investigate additional measures of autonomic response as well as other sources of persistent fatigue, in these individuals.