The Orexin System and Its Impact on the Autonomic Nervous and Cardiometabolic System in Post-Acute Sequelae of COVID-19

Orexins (OXs) are critical for regulating circadian rhythms, arousal, appetite, energy metabolism, and electrolyte balance, affecting both the autonomic nervous system (ANS) and the cardiovascular system (CVS). Disruption of the OX system can result in symptoms similar to those observed in post-acute sequelae of COVID-19 (PASC). This review emphasizes the adverse effects of OX dysregulation on autonomic and cardiometabolic functions in patients with PASC. Additionally, we highlight the potential of anti-OX therapies to provide neuroprotective, anti-inflammatory, and immunoregulatory benefits, offering hope for alleviating some of the debilitating symptoms associated with PASC.