Impact of Post-COVID-19 Status on Autonomic Function, Hypothalamic-Pituitary-Adrenal (HPA) Axis Activity and Psychological Status

Abstract Purpose COVID-19 may be associated with long-term alterations in integrated stress-regulatory systems, including the autonomic nervous system and the hypothalamic–pituitary–adrenal (HPA) axis. This study evaluated ANS and HPA axis activity together with psychological status in individuals with post-COVID status. Methods This cross-sectional study included 97 university students aged 18–30 years: 37 with a history of COVID-19 (13 females, 24 males) and 60 without prior infection (17 females, 43 males). Post-COVID assessments were conducted approximately two years after infection. Autonomic function was assessed using 5-minute heart rate variability (HRV) recordings (HR, SDNN, RMSSD, pNN50, TP, HF, LF, VLF, LF/HF). HPA axis activity was evaluated by salivary cortisol measured with ELISA. Psychological status was assessed using the State–Trait Anxiety Inventory (STAI-I/II) and the Pittsburgh Sleep Quality Index (PSQI). Blood pressure, oxygen saturation, and body temperature were also recorded. Results HRV parameters did not differ between the groups ( p > 0.05). Salivary cortisol levels were higher in individuals with a history of COVID-19 compared to controls ( p = 0.042). STAI-I ( p = 0.810), STAI-II ( p = 0.130), and Pittsburgh Sleep Quality Index (PSQI) scores ( p = 0.157) were comparable between post-COVID individuals and controls. Mean blood pressure values were similar across groups; however, diastolic blood pressure was lower in female participants with a history of COVID-19 ( p = 0.036). Body temperature ( p = 0.084) and peripheral oxygen saturation (SpO₂) ( p = 0.542) were also comparable between groups. Conclusion Post-COVID status appears to be associated with increased HPA axis activity despite preserved autonomic function and psychological status. The persistence of elevated cortisol levels nearly two years after infection suggests that COVID-19 may exert long-lasting effects on the stress response system. These findings indicate that the impact of the disease may extend beyond the acute phase and involve sustained neuroendocrine alterations.