Author(s): BESSON, C., MACHADO RIBEIRO, J., BAGGISH, A.L., MOSER, M., CASSOLI, I., GREMEAUX, V., SAUBADE, M., Institution: CHUV LAUSANNE, Country: SWITZERLAND, Abstract-ID: 865

INTRODUCTION:
Long COVID is frequently associated with persistent fatigue, reduced exercise tolerance, and symptoms suggestive of autonomic nervous system dysregulation. Heart rate variability (HRV) is commonly used to assess cardiac autonomic function in health, exercise, and disease. However, HRV findings in Long COVID remain heterogeneous, partly due to methodological variability and the frequent use of single-position resting measurements that do not capture autonomic regulation relevant to active orthostatic testing. The purpose of this study was to compare short-term HRV measured in supine and standing positions between Long COVID patients and physically active healthy controls, and to characterize autonomic regulation during active orthostatic testing.
METHODS:
Fifty Long COVID patients (median age 40.5 years, 74 % women) and forty-six physically active healthy controls (median age 32.0 years, 48 % women) performed standardized short-term HRV recordings at awakening. HRV was recorded for five minutes in the supine position followed by five minutes during active standing using a chest strap heart rate monitor. Time-domain (heart rate, RMSSD) and frequency-domain variables were extracted from the final four minutes of each recording. Group comparisons were performed using unadjusted analyses (Wilcoxon test) and adjusted for age and sex using a doubly robust estimator based on inverse-probability-of-treatment-weighting (IPTW) combined with linear regression.
RESULTS:
After adjustment for age and sex, Long COVID patients exhibited higher heart rate in the supine position (adjusted mean difference: +6.7 bpm, 95% Confidence Interval [CI]: 3.1 to 10.3, p < 0.001) and during standing (+8.3 bpm, 95% CI: 3.6 to 12.9, p < 0.001). At rest, parasympathetic modulation was reduced in Long COVID patients, with lower log-transformed RMSSD (adjusted difference: -0.20, 95% CI: -0.20 to -0.10, p < 0.001) and lower log-transformed high-frequency power (adjusted difference: -0.20, 95% CI: -0.40 to -0.03, p = 0.019). During standing, Long COVID patients showed a lower low-frequency power relative to heart rate (adjusted difference: -5.5, 95% CI: -10.5 to -0.5, p = 0.030), indicating altered autonomic regulation during active orthostatic testing rather than a uniform increase in sympathetic modulation. Individual responses revealed heterogeneous autonomic patterns, including preserved or elevated parasympathetic indices at rest in a subset of patients.
CONCLUSION:
Long COVID is associated with a combination of reduced parasympathetic modulation at rest and altered autonomic regulation during active orthostatic testing. Assessing HRV under standardized conditions in both supine and standing positions provides qualitative insight into dynamic autonomic control that is not captured by resting measurements alone. This approach may help to better understand fatigue and exercise intolerance in Long COVID and supports the relevance of dynamic autonomic assessment for health and fitness evaluation in this population.