Post-covid syndrome (PCS) is a condition with manifold symptoms some of which are related to a dysregulation of the autonomic nerve system such as inappropriate sinus tachycardia, orthostatic symptoms without tachycardia or hypotension and postural tachycardia syndrome. Measuring heart rate variability may serve as a surrogate for cardiac autonomic activity in PCS.

Methods

We report on the results of a prospective observational cohort study of patients referred to medical rehabilitation due to a diagnosis of PCS. One hundred and three PCS patients fulfilled the eligibility criteria after detailed clinical screening. The median time interval between the acute COVID-19 infection and start of medical rehabilitation was 252 days. During acute infection, 31% had been hospitalized, 69% had received ambulant care or acute care at home. Patients underwent CPET and 24-h Holter monitoring. Impact of disease was evaluated by questionnaires. Comparisons were made between PCS patients and patients with CAD (n=103) enrolled during medical rehabilitation. A healthy control group was included for comparison of HRV data. 

Results

Mean relative peak exercise O₂ uptake in PCS patients was reduced by almost 30% and was comparable to the reduced relative peak exercise O₂ uptake of CAD patients (72.7 ± 16.8% vs.75.5 ± 16.0%, p=0.290). PCS Patients’ general wellbeing was lower compared to CAD patients (p<0.001) and health-related quality of life was significantly reduced, indicated by SF-36 questionnaire (p≤0.002) and assessment of Workability Index. A number of frequency-related variables were detected to differ significantly in PCS patients compared to controls including LF power, LF nu, HF power, HF nu, and LF/HF ratio (24h period; p≤0.001). In contrast, there was no difference in these parameters between PCS and CAD patients. Of note, sympathicus activation as reflected by LF/HF ration and percentage of sympathicus and parasympathicus was highest in PCS patients compared to controls and CAD patients during the 24-h period. With regard to non-linear variables, VAI 24h was significantly reduced with PCS, compared to both CAD patients and controls (p≤0.001) while SD1 24h was comparable to controls but lower than in CAD patients (p=0.037). Compared to controls the day-night shift of HFnu and LFnu was abolished showing no increase of parasympathetic activity during night. The analysis suggested further that longer persistence of PCS symptoms (i. e. time after acute infection) significantly affected predominantly frequency-related variables with a decline of sympathetic stimulation. In contrast, the need for hospitalization (after correction for age) also affected time-related HRV variables.

Conclusion

In summary, we demonstrate HRV alterations in PCS patients with long-term symptom duration, which might reflect an impaired sympatho-vagal balance. There were signs of a sympathetic overstimulation and a diminished parasympathetic response comparable to findings in CAD patients. The relation of these HRV anomalies to the severity of the acute Covid-19 infection supports their relevance. Whether HRV variables might have a prognostic value for PCS and/or might serve as biomarkers during a successful interventional approach warrants further longitudinal studies.