Baroreflex sensitivity impairment in Long-COVID patients: a diagnostic tool for classifying the autonomic dysfunction spectrum

Long-COVID describes a variety of COVID-19 side effects lasting longer than three months. Among these side effects are cardiovascular alterations, such as Postural Orthostatic Tachycardia Syndrome (POTS), caused by an autonomic nervous system dysfunction. A higher incidence of POTS and decreased baroreceptor sensitivity (BRS) has been reported in Long-COVID patients. Many of these patients present orthostatic intolerance similar to that observed in POTS, which does not strictly coincide with the criteria that have previously been established for POTS subtypes. Therefore, we aim to determine if the decrease of the baroreceptor sensitivity is enough to diagnose different degrees of the autonomic dysfunction spectrum. A cross-sectional study was conducted in a cohort of individuals who presented with various long-term symptoms for at least four weeks after a moderate acute COVID-19 infection. To further evaluate orthostatic intolerance (OI), we developed a new method that enables a more detailed characterization of cardiovascular dynamics using beat-to-beat physiological time series. Since these dynamics can be assessed through the measurement of baroreceptor sensitivity, this new method employs a geometric analysis that reveals varying degrees of baroreceptor sensitivity impairment. The proposed method generated a graph of baroreflex sensitivity that consistently showed a decrease in this index. Patients exhibited significantly lower BRS compared with healthy controls during orthostatism. Furthermore, we noticed that patients with lower BRS had a significantly higher arterial blood pressure and heart rate, as well as an overall lower heart rate variability. The proposed method also correlated with previously recognized canonical variables of HRV, as well as being validated with the sequence method. Additionally, this allows us to understand and reclassify patients' diagnoses within the spectrum of symptoms similar to postural orthostatic tachycardia syndrome (POTS). The proposed method allowed us to consider this decrease in baroreflex sensitivity measurement as a diagnostic tool through a spectrum-based approach to reclassify patients. This analysis can be incorporated into the set of variables considered to improve the diagnosis of patients with Long-COVID.