Longitudinal Trajectory of Post-COVID Sleep Disturbance and its Relationship With Other Long-COVID Symptoms
Kijeong Kim1, Dayoung Seo1, Yangsean Choi2, EUNSEON JEONG3, Hee Jae Jung1, Sanghwi Bang1, In-Hye Jang1, lynkyung choi1, JIN HEE KIM1, Bo-Ra Seo1, Hyunjin Kim1, Young-Min Lim1, Eun-Jae Lee1
1Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, 2Department of Radiology, Asan Medical Center, University of Ulsan College of Medicine, 3Asan Medical Institute of Convergence Science and Technology, University of Ulsan College of Medicine
Objective:

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.

Background:

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.

Design/Methods:

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.

Results:
At baseline, 161 (81%) individuals exhibited sleep disturbance (PSQI-K > 5), and 93% of people with PASC reported concurrent sleep problems. Although PSQI-K scores improved gradually over 12 months, 125 (77%) continued to experience persistent sleep disturbance. Higher PSQI-K scores showed a positive correlation with PASC scores (r= 0.851, p <0.001) and were particularly associated with fatigue, palpitations, and cognitive complaints. Serum proteomic analysis did not distinguish sleep disturbance with or without PASC, suggesting shared systemic mechanisms rather than distinct molecular profiles. Structural MRI changes in the choroid plexus, cingulate, and amygdala were observed in participants with PASC but were not specific to sleep disturbance.
Conclusions:

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.

10.1212/WNL.0000000000215793
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