Neurological Institute Outcomes

Post-Acute Sequelae of SARS-CoV-2 (PASC) poses a global public health challenge, manifesting in persistent sleep disturbances beyond 4 weeks post-acute infection. Despite the high prevalence of PASC-related sleep symptoms, there is a lack of objective evidence, particularly in sleep study characterization of reported sleep disturbances. The objective was to identify distinct sleep study features of PASC-related symptoms.

The Sleep Center conducted a retrospective cohort study of patients presenting with PASC to the ReCOVer Clinic between February 2021 and May 2023. It included patients with PASC who completed PROMIS-Sleep Disturbance questionnaires and underwent sleep studies following a positive COVID test. Sleep study variables and PASC-specific symptoms were compared by PROMIS-Sleep Disturbance. Moderate-severe Sleep Disturbance was indicated by a T-score of ≥60. Multivariable logistic regression models were used to predict moderate-severe Sleep Disturbance based on demographics, sleep study indices, and PASC symptoms. Statistical interactions of sleep study indices by sex and race were examined.

The study included 365 patients. Of those, 45% (N=166) reported moderate-severe Sleep Disturbance. These patients were 48±12 years of age, 77% female, 71% white, 19% black, had body mass of 35±9 kg/m², 22% (N=34) were hospitalized for COVID-19. These patients differed from those with normal or mild Sleep Disturbances by race (p=0.02) in that they were more likely to be Black; there were no differences in age, sex, body mass index, or hospitalization status. Less rapid eye movement (REM) sleep was a significant predictor of moderate-severe Sleep Disturbance (OR=0.95, 95% CI=0.92-0.99, p=0.01). Males with moderate-sever Sleep Disturbance exhibited higher average heart rate during sleep. PASC symptoms that were more common in moderate-severe Sleep Disturbance vs. normal or mild Sleep Disturbance included: dyspnea (75% vs. 61%, p=0.008), joint aches/pains (48% vs 31%, p=0.04), and headaches (48% vs 33%, p=0.03).

The sleep architectural alteration of lower percentage of REM sleep is associated with a greater degree of patient-reported sleep disturbance in PASC. Males experiencing moderate-severe Sleep Disturbance showed elevated heart rate during sleep, potentially reflecting sleep-related autonomic dysfunction in PASC. PASC-specific symptoms of dyspnea, joint pain, and headaches appear to be clinically relevant sleep disruptors in recurrent PASC. Future investigation should focus on enhanced understanding of REM sleep-specific neural circuitry and memory consolidation in PASC as well as sleep-related autonomic fluctuations. Targeting treatment of specific PASC symptoms such as dyspnea and pain may mitigate compromise in sleep and improve clinical outcomes.

Sleep difficulties and fatigue are prevalent, pervasive symptoms reported in patients with Post-Acute Sequelae of COVID-19 (PASC). PROMIS scores are standardized to the general U.S. adult population on a T-scale with a mean of 50±10. PROMIS Sleep Disturbance and Fatigue T-scores ≥60 indicate at least moderate disturbance and ≥70 indicate severe disturbance.

Of 1,321 patients seen at the Cleveland Clinic ReCOVer Clinic (February to November 2021), 682 completed the PROMIS Sleep Disturbance questionnaire (ages 49.8 ± 13.6, 75.2% were female, and 12.3% were Black race). Average T-scores were 57.7 ± 8.3; 281 (41.2%) patients reported at least moderate sleep disturbance and 50 (7.3%) reported severe sleep disturbances. Average PROMIS Fatigue T-score (n=636) was 63 ± 9.1, of which 68.6% (n=436) reported at least moderate fatigue and 22.6% (n=144) reported severe fatigue.

Patients with moderate-severe sleep disturbances had higher BMI (32.3 ± 8.7 vs 30.9 ± 7.5 kg/m², P = 0.049), were Black race (15.7% vs 10.0%, P = 0.010), and had worse general anxiety disorder (GAD)-2 questionnaire scores (2.8 ± 2.1 vs 1.6 ± 1.7, P < 0.001), Patient Health Questionnaire (PHQ)-2 scores (2.8 ± 2 vs 1.6 ± 1.7, P < 0.001), and PROMIS fatigue scores (66.7 ± 7.8 vs 60.4 ± 9.1, P < 0.001), with no difference in age, sex, or hospitalization due to COVID-19 compared to patients with no or mild sleep disturbance. In the adjusted model, Black race was associated with moderate-severe sleep disturbance (OR = 3.42, 95% CI, 1.64-7.13). To summarize, the prevalence of moderate-severe sleep disturbance reported by patients presenting for PASC was >40% and associated with obesity, Black race, and mood symptoms.