코로나 후유증으로서 장기적 수면의 질 연구 = Longitudinal Sleep Quality in Long COVID

다국어 초록 (Multilingual Abstract)

Objectives
This study aimed to investigate the longitudinal course of sleep disturbances after COVID-19 infection, explore their association with post-acute sequelae of SARS-CoV-2 infection (PASC), and identify potential serum and neuro-imaging biomarkers.

Background
Sleep disturbance is one of the most prevalent neurological manifestations of PASC. However, its long-term trajectory and biological mechanisms remain unclear. Understanding whether post- COVID sleep disturbance represents a symptom of PASC or a distinct sequela is necessary for targeted management and prognosis.

Methods
In this prospective, longitudinal observational study, 198 adults previously infected with SARS- CoV-2 were followed for one year. Sleep quality was assessed using the Korean version of the Pittsburgh Sleep Quality Index (PSQI-K) at baseline and every three months. PASC was defined by a symptom-based scoring system. Blood biomarkers were analyzed using Single Molecule Array and Olink proteomics. Brain MRI was performed at baseline to measure cortical thickness, regional volumes, and the ALPS index.

Results
At baseline, 81% of participants exhibited sleep disturbances (PSQI-K > 5). Among those with sleep disturbances, 28.6% met the criteria for PASC, whereas 93% of participants with PASC reported sleep disturbances. Over 12 months, PSQI-K scores improved, though more than 70% of participants continued to experience sleep disturbance. Among participants with sleep disturbances, those with PASC had higher baseline severity of sleep disturbance and showed a greater tendency for persistence of symptoms at the one-year follow-up. No significant differences in Simoa biomarkers and Olink proteomics were observed according to the presence of sleep disturbance or PASC status. Among participants with sleep disturbances, those with PASC showed reduced choroid plexus, cingulate, and amygdala volumes on baseline brain MRI.

Conclusions
In a Korean post-COVID cohort, sleep disturbance remained highly prevalent even more than one year after infection, and participants with PASC experienced more severe and prolonged sleep disturbances. Considering the strong association between sleep disturbance and PASC, along with the biomarker findings, post-COVID sleep disturbance should be viewed as a continuum related to PASC.

목차 (Table of Contents)

• 1. Introduction 1
• 2. Method 3
• i. Study Design 3
• ii. PASC Definition 3
• iii. PSQI Score 3
• iv. Measures 3
• v. Blood Sampling 4
• vi. Neuroimaging 4
• vii. Statistical Analysis 4
• 3. Results 6
• i. Study Population and Baseline Characteristics 6
• ii. Sleep Disturbance and other neuropsychiatric symptoms 6
• iii. Trajectory of PSQI Scores Over Time 6
• iv. Serum Biomarkers 7
• v. Neuroimaging Biomarkers 7
• 4. Discussion 8
• i. Characteristics of Post-COVID Sleep Disturbances 8
• ii. Association Between Post-COVID Sleep Disturbances and PASC 9
• iii. Biomarker Analysis in Post-COVID Sleep Disturbance and PASC 10
• iv. Study Limitations 11
• 5. Conclusion 13
• 6. Figure 14
• i. Figure 1: Linear Regression Between PSQI-K and Questionnaire Scores 14
• ii. Figure 2: Longitudinal Changes in PSQI Among Participants with Sleep Disturbances 15
• iii. Figure 3: Predicted PSQI-K Score Over Time by PASC 16
• iv. Figure 4: Volcano Plot of DEPs According to PASC Status Among Participants With Sleep Disturbance 17
• v. Figure 5: Gene Ontology Analysis in PASC According to PASC Status Among Participants With Sleep Disturbance 18
• 7. Table 19
• i. Table 1: Baseline Characteristics and Comparison Between Participants With and Without Sleep Disturbance 19
• ii. Table 2: Sleep Disturbance and Questionnaire Scores 21
• iii. Table 3: Simoa Assay Results by Sleep Disturbance Status 22
• iv. Table 4: Simoa Assay Results by PASC Among Participants With Sleep Disturbance 23
• v. Table 5: Comparison of Brain MRI Biomarkers According to Sleep Disturbance and PASC Status Among Sleep Disturbance at Baseline 24
• vi. Table 6: Comparison of Brain MRI Biomarkers According to PASC Status Among Participants With Sleep Disturbance at 1-Year Follow-up 25
• 8. Reference 26