SARS-CoV-2 alters neural synchronies in the brain with more severe effects in younger individuals.

Coronavirus disease secondary to infection by SARS-CoV-2 (COVID19 or C19) causes respiratory illness, as well as severe neurological symptoms that have not been fully characterized. In a previous study, we developed a computational pipeline for the automated, rapid, high-throughput and objective analysis of electroencephalography (EEG) rhythms. In this retrospective study, we used this pipeline to define the quantitative EEG changes in patients with a PCR-positive diagnosis of C19 (n = 31) in the intensive care unit (ICU) of Cleveland Clinic, compared to a group of age-matched PCR-negative (n = 38) control patients in the same ICU setting. Qualitative assessment of EEG by two independent teams of electroencephalographers confirmed prior reports with regards to the high prevalence of diffuse encephalopathy in C19 patients, although the diagnosis of encephalopathy was inconsistent between teams. Quantitative analysis of EEG showed distinct slowing of brain rhythms in C19 patients compared to control (enhanced delta power and attenuated alpha-beta power). Surprisingly, these C19-related changes in EEG power were more prominent in patients below age 70. Moreover, machine learning algorithms showed consistently higher accuracy in the binary classification of patients as C19 versus control using EEG power for subjects below age 70 compared to older ones, providing further evidence for the more severe impact of SARS-CoV-2 on brain rhythms in younger individuals irrespective of PCR diagnosis or symptomatology, and raising concerns over potential long-term effects of C19 on brain physiology in the adult population and the utility of EEG monitoring in C19 patients.

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)  

Health-Related Quality of Life Mildly Affected Following COVID-19: a Retrospective Pre-post Cohort Study with a Propensity Score-Matched Control Group.

IMPORTANCE: Long-term health effects have been indicated following COVID-19; however, the impact of COVID-19 on health-related quality of life (HRQOL), including who may experience ongoing symptoms, is unknown. OBJECTIVE: To identify change in HRQOL following COVID-19 compared to pre-infection HRQOL and a matched control group, and identify predictors of patients who worsen. DESIGN: Retrospective pre-post cohort study with a matched control group. SETTING: Large healthcare system in northeast Ohio. PARTICIPANTS: A total of 3,690 adult patients diagnosed with COVID-19 who completed HRQOL surveys during routine care for ambulatory visits before and after infection. Propensity-score 1:1 match was utilized to identify controls without COVID who completed HRQOL at two time points. MAIN OUTCOMES: HRQOL was assessed with PROMIS Global Health: global mental and physical health summary scores. Pre- and post-COVID PROMIS Global Health was completed as part of routine care from 1/1/2019 to 2/29/2020 and 4/4/2020 to 11/1/2021, respectively, and extracted from the electronic health record. RESULTS: COVID-19 patients (mean age 53±15; 66% female) completed PROMIS Global Health in the year prior (median 11.1 months) and after diagnosis (median 7.8 months). Compared to before infection, COVID-19 patients had a significant reduction in global mental health and stable global physical health (-0.85 and 0.05 T-score points, respectively) with clinically meaningful reduction (≥5 T-score points) experienced by 27% and 23% of patients, respectively. Predictors of worsening global health included being female, having depression, being hospitalized for COVID-19, and better pre-COVID global health. Compared to the control group, there was significantly worse global mental and physical health decline following COVID-19 (-0.53 and -0.37 T-score points, respectively). CONCLUSIONS AND RELEVANCE: A quarter of patients with COVID-19 experienced meaningful reductions in HRQOL. Reductions in global mental and physical health were modest, although significantly worse than a control group. Additionally, identified predictors of patients who worsen may assist clinicians when counseling patients of their risk of worse HRQOL following COVID-19.

Evidence of Stability in Patient-Reported Global Health During the COVID-19 Pandemic.

OBJECTIVES: Measures of health-related quality of life (HRQOL) are collected throughout healthcare systems and used in clinical, economic, and outcomes studies to direct patient-centered care and inform health policy. Studies have demonstrated increases in stressors unique to the COVID-19 pandemic, however, their effect on HRQOL is unknown. Our study aimed to assess the change in self-reported global health during the pandemic for patients receiving care in a large healthcare system compared with 1 year earlier. METHODS: An observational cross-sectional study of 2 periods was conducted including adult patients who had a healthcare appointment and completed the Patient-Reported Outcomes Measurement Information System Global Health (PROMIS GH) as standard care during the COVID-19 pandemic and a year earlier. The effect of time on PROMIS global mental health (GMH) and global physical health (GPH) was evaluated through multiple statistical methods. RESULTS: There were 38 037 patients (mean age 56.1 ± 16.6 years; 61% female; 87% white) who completed the PROMIS GH during the pandemic (August 2020) and 33 080 (age 56.7 ± 16.5 years; 61% female; 86% white) who had completed it 1 year earlier (August 2019). GMH was significantly worse, whereas GPH was similar during the pandemic compared with a year earlier (adjusted estimate [standard error]: -1.21 (0.08) and 0.11 (0.08) T-score points, respectively). CONCLUSIONS: Our study found modest, nonclinically meaningful decreases in GMH and similar GPH during the COVID-19 pandemic compared with a year earlier in patients cared for in a large healthcare system. Nevertheless, healthcare systems are likely seeing a biased sample of patients during these times. Findings from our study have implications for the interpretation of HRQOL during this pandemic.

Frequency of Physical Therapist Intervention Is Associated With Mobility Status and Disposition at Hospital Discharge for Patients With COVID-19.

OBJECTIVE: For patients diagnosed with the novel coronavirus, COVID-19, evidence is needed to understand the effect of treatment by physical therapists in the acute hospital on patient outcomes. The primary aims of this study were to examine the relationship of physical therapy visit frequency and duration in the hospital with patients' mobility status at discharge and probability of discharging home. METHODS: This retrospective study included patients with COVID-19 admitted to any of 11 hospitals in 1 health system. The primary outcome was mobility status at discharge, measured using the Activity Measure for Post-Acute Care 6-Clicks basic mobility (6-Clicks mobility) and the Johns Hopkins Highest Level of Mobility scales. Discharge to home versus to a facility was a secondary outcome. Associations between these outcomes and physical therapy visit frequency or mean duration were tested using multiple linear or modified Poisson regression. Potential moderation of these relationships by particular patient characteristics was examined using interaction terms in subsequent regression models. RESULTS: For the 312 patients included, increased physical therapy visit frequency was associated with higher 6-Clicks mobility (b = 3.63; 95% CI, 1.54-5.71) and Johns Hopkins Highest Level of Mobility scores (b = 1.15; 95% CI, 0.37-1.93) at hospital discharge and with increased probability of discharging home (adjusted relative risk = 1.82; 95% CI, 1.25-2.63). Longer mean visit duration was also associated with improved mobility at discharge and the probability of discharging home, though the effects were less pronounced. Few moderation effects were observed. CONCLUSION: Patients with COVID-19 demonstrated improved mobility at hospital discharge and higher probability of discharging home with increased frequency and longer mean duration of physical therapy visits. These associations were not generally moderated by patient characteristics. IMPACT: Physical therapy should be an integral component of care for patients hospitalized due to COVID-19. Providing sufficient physical therapist interventions to improve outcomes must be balanced against protection from viral spread. LAY SUMMARY: Patients with COVID-19 can benefit from more frequent and longer physical therapy visits in the hospital.