Abstract

Abstract Introduction Fatigue and sleep disturbance are among the most common neurological post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC). We tested the hypothesis that impaired sleep and disrupted rest-activity rhythms are associated with impaired cognitive performance and greater burden of self-reported Neuro-PASC symptoms. Methods Forty adults (mean age 45 years, 69% female, 15% hospitalized post COVID) recruited from the Neuro-COVID-19 Clinic at Northwestern Memorial Hospital. Patients were evaluated via clinical assessment/history, chart review, patient reported outcomes for symptom severity (PROMIS cognitive function, fatigue, sleep disturbance, anxiety, depression), cognitive performance tests (NIH Toolbox modules for processing speed, attention, executive function, working memory), and 7 days of wrist actigraphy with a sleep log. We tested associations between objective and subjective measures using Pearson’s correlation and difference from population normative data using Student’s t test. Results 39 participants provided sufficient data for analysis. The median number of discrete neurologic symptoms attributed to PASC was 6 with 87% reporting ≥4 neurologic symptoms. Fatigue, insomnia, and depression were common (~70% reporting each). Participants reported significant symptom burden in all PROMIS domains, and had measurably worse attention function along with borderline executive function, compared to population normative data (all p< 0.001 except executive cognition p=0.056). Actigraphy showed Neuro-PASC patients had lower sleep efficiency and greater sleep latency (both p< 0.001) but similar wakefulness after sleep onset (WASO) compared to age-matched population controls. Self-reported cognitive symptoms were correlated with severity of fatigue (p< 0.001), anxiety (p=0.05), and depression (p< 0.01), but not subjective sleep disturbance. There were no associations between actigraphy-measured sleep or rest-activity characteristics and self-reported symptoms. Patients with abnormal sleep characteristics (WASO, sleep efficiency, sleep latency) demonstrated impaired objective attention and executive function. Conclusion Neuro-PASC patients presenting to a post-COVID clinic have a significant burden of subjective mental health, sleep, fatigue and cognitive impairment symptoms, along with objectively abnormal cognitive performance and sleep, compared to population controls. Interventions to improve sleep could benefit cognitive performance. Prospective studies including larger populations of patients are needed to fully determine the interplay of sleep/circadian rhythm disruption on the cognitive function and quality of life in patients with PASC. Support (if any) Center for Circadian and Sleep Medicine

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