Sleep Disturbances in Post-Acute Sequelae of COVID-19 (PASC)

Introduction Sleep difficulties and fatigue are highly prevalent, pervasive symptoms reported in patients with Post-Acute Sequelae of COVID-19 (PASC). As little is known of the predictors and severity of PASC-related sleep disturbance and intersection with fatigue, we leverage systematic data collected from the Cleveland Clinic ReCOVer Clinic for further elucidation Methods Analysis of data collected from Cleveland Clinic ReCOVer Clinic patients (February-November 2021) who completed the Patient-Reported Outcomes Measurement (PROMIS) Sleep Disturbance and PROMIS Fatigue questionnaires was performed. Data were extracted from the Cleveland Clinic COVID-19 registry and the electronic health record.PROMIS scores are standardized to the general U.S. adult population on a T-scale with mean 50±10. PROMIS sleep disturbance and fatigue T-scores ≥60 indicates at least moderate disturbance and ≥70 indicate severe disturbance. T-test and Chi-square tests were used to examine cross-group differences. Multivariable logistic regression adjusted for age, race, sex, and body mass index(kg/m2) was performed to investigate factors associated with sleep disturbance severity. Results Out of 1321, 682 patients completed the PROMIS Sleep Disturbance questionnaire with age 49.8±13.6, 75.2% female and 12.3% 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 was 63.0±9.2;68.6% patients reported at least moderate fatigue, 22.6% reported severe fatigue. Patients with moderate-severe compared to normal-to-mild sleep disturbances respectively had higher BMI (32.3±8.7 vs 30.9±7.5, p=0.049), were more likely of black race (40.0±10.0 vs 41.0±15.7,p=0.010), had worse eneral Anxiety Disorder (GAD)-2 questionnaires scores (2.8±2.1 vs 1.6±1.7,p<0.001), Patient Health Questionnaire (PHQ)-2 scores (2.8±2.0 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. In the adjusted model, black race was associated with moderate-severe sleep disturbance (OR=3.42, 95%CI:1.64-7.13). Conclusion The prevalence of moderate to severe sleep disturbances reported by patients presenting for PASC was very high i.e.>40% and associated with obesity, black race and mood symptoms. Notably, after adjustment for demographics, black race conferred a 3-fold higher odds of moderate-severe sleep disturbance emphasizing the need to characterize race-specific determinants and disparities in COVID-19 survivors. Support (If Any)  

Association of Sleep-Related Hypoxia With Risk of COVID-19 Hospitalizations and Mortality in a Large Integrated Health System.

Importance: The influence of sleep-disordered breathing (SDB) and sleep-related hypoxemia in SARS-CoV-2 viral infection and COVID-19 outcomes remains unknown. Controversy exists regarding whether to continue treatment for SDB with positive airway pressure given concern for aerosolization with limited data to inform professional society recommendations. Objective: To investigate the association of SDB (identified via polysomnogram) and sleep-related hypoxia with (1) SARS-CoV-2 positivity and (2) World Health Organization (WHO)-designated COVID-19 clinical outcomes while accounting for confounding including obesity, underlying cardiopulmonary disease, cancer, and smoking history. Design, Setting, and Participants: This case-control study was conducted within the Cleveland Clinic Health System (Ohio and Florida) and included all patients who were tested for COVID-19 between March 8 and November 30, 2020, and who had an available sleep study record. Sleep indices and SARS-CoV-2 positivity were assessed with overlap propensity score weighting, and COVID-19 clinical outcomes were assessed using the institutional registry. Exposures: Sleep study-identified SDB (defined by frequency of apneas and hypopneas using the Apnea-Hypopnea Index [AHI]) and sleep-related hypoxemia (percentage of total sleep time at <90% oxygen saturation [TST <90]). Main Outcomes and Measures: Outcomes were SARS-CoV-2 infection and WHO-designated COVID-19 clinical outcomes (hospitalization, use of supplemental oxygen, noninvasive ventilation, mechanical ventilation or extracorporeal membrane oxygenation, and death). Results: Of 350 710 individuals tested for SARS-CoV-2, 5402 (mean [SD] age, 56.4 [14.5] years; 3005 women [55.6%]) had a prior sleep study, of whom 1935 (35.8%) tested positive for SARS-CoV-2. Of the 5402 participants, 1696 were Black (31.4%), 3259 were White (60.3%), and 822 were of other race or ethnicity (15.2%). Patients who were positive vs negative for SARS-CoV-2 had a higher AHI score (median, 16.2 events/h [IQR, 6.1-39.5 events/h] vs 13.6 events/h [IQR, 5.5-33.6 events/h]; P < .001) and increased TST <90 (median, 1.8% sleep time [IQR, 0.10%-12.8% sleep time] vs 1.4% sleep time [IQR, 0.10%-10.8% sleep time]; P = .02). After overlap propensity score-weighted logistic regression, no SDB measures were associated with SARS-CoV-2 positivity. Median TST <90 was associated with the WHO-designated COVID-19 ordinal clinical outcome scale (adjusted odds ratio, 1.39; 95% CI, 1.10-1.74; P = .005). Time-to-event analyses showed sleep-related hypoxia associated with a 31% higher rate of hospitalization and mortality (adjusted hazard ratio, 1.31; 95% CI, 1.08-1.57; P = .005). Conclusions and Relevance: In this case-control study, SDB and sleep-related hypoxia were not associated with increased SARS-CoV-2 positivity; however, once patients were infected with SARS-CoV-2, sleep-related hypoxia was an associated risk factor for detrimental COVID-19 outcomes.