To characterize the longitudinal course of sleep disturbance after COVID-19 infection and to explore its relationship with post-acute sequelae of SARS-CoV-2 infection (PASC) and potential biomarkers.

Sleep disturbance is common neurological symptoms following COVID-19 infection, frequently co-occurring with fatigue and cognitive complaints. However, whether post-COVID sleep disturbance represents an independent sequela or a manifestation of the broader neuro-PASC process remains unclear. Understanding its long-term trajectory and biological correlates is essential for improving post-COVID care.

This prospective longitudinal study included 198 adults approximately one year after mild COVID-19 infection. Sleep quality was assessed every three months using the Korean version of the Pittsburgh Sleep Quality Index (PSQI-K). PASC severity was quantified using a symptom-based scoring system. Serum biomarkers (3072 proteins) were analyzed using the Olink Explore platform, and brain MRI was performed at baseline to assess cortical thickness, regional volumes, and the DTI–ALPS index.

Sleep disturbance is highly prevalent and interlinked with the overall burden of PASC, rather than representing an isolated sequela. Considering more than 70% of participants continued to experience sleep problems one year after infection, these findings underscore the need for ongoing clinical attention and personalized management strategies to support long-term post-COVID recovery.