Abstract
Post-COVID syndrome (long COVID) is increasingly recognized as a state of chronic inflammation, immune imbalance, and multiorgan dysfunction. Emerging evidence highlights circadian rhythm disruption and melatonin dysregulation as overlooked drivers of persistent symptoms such as fatigue, cognitive impairment, and immune dysregulation. Reduced melatonin impairs cytokine suppression, antioxidant defense, and mitochondrial protection, fueling inflammation and oxidative stress. These disruptions, coupled with autoimmune responses targeting adrenergic and muscarinic receptors, exacerbate systemic pathology. Preliminary data suggest that melatonin supplementation and chronotherapy may restore circadian alignment, rebalance immunity, and mitigate disease progression, although robust large-scale trials remain limited. Integrating circadian science into therapeutic protocols may provide a novel avenue for improving long-term outcomes in post-COVID patients.