Reduced autonomic function in patients with long-COVID-19 syndrome is mediated by cardiorespiratory fitness

Abstract

Background: Long-COVID-19 syndrome (LCS) exhibits neurological problems such as peripheral neuropathy and autonomic nervous system (ANS) dysfunction. Exercise intolerance and, consequently, low cardiorespiratory fitness (CRF) are some of the most common symptoms of LCS. We describe a series of individuals exhibiting LCS symptoms compared to a control group and posit that this condition may be related to the exercise capacity-mediated disruption of the ANS resulting particularly in exercise intolerance.

Methods: This study included 87 individuals with LCS and 71 control participants without COVID-19 diagnoses. Heart rate variability (HRV) in supine position is commonly measured to diagnose autonomic dysregulation and subsequently analyzed using the Kubios software (Kuopio, Finland). CRF (peak VO₂), post-COVID-19 patient-reported symptoms, maximal muscle strength (grip strength, bilateral leg press, leg extension, pectoral press, and back press exercises), and body composition were also measured. Analysis of covariance (ANCOVA) and mediation analysis were employed to assess the associations among LCS, peak VO₂, and HRV indicators. Two-sided p < 0.05 was considered as significant.

Results: The HRV parameters-RR interval, RMSSD, SDNN, PNS index, LF, HF, total power, SD1, and SD2-were significantly elevated (p < 0.05) in the control group when compared to the LCS patients. In contrast, the HR, stress index, and SNS index parameters were significantly higher (p < 0.05) in the LCS group. When adjusted for RR intervals, these parameters remained statistically significant (p < 0.05). A partially mediated effect was found between peak VO₂ and RMSSD (mediation effect = 24.4%) as well as peak VO₂ and SDNN (mediation effect = 25.1%) in the LCS patients.

Conclusions: These findings contribute new insights on the interplay between CRF and HRV indicators as well as endorse that dysautonomia may be related to the low peak VO₂ observed in long COVID-19 patients.

Keywords: Autonomic function; Long-COVID-19 syndrome; Physical condition; Post-acute COVID-19 syndrome.