Pathogenic Mechanisms of Neuro-PASC in Older Adults

Introduction: The study focus is to better understand the interplay of sleep dysfunction and fatigue in cognitive function of Long COVID patients.

Objective: We performed a multidimensional analysis of mood, cognition, sleep and circadian rhythms in patients with post-acute sequelae of SARS-CoV-2 (PASC) infection with the objective of characterizing the phenotype of PASC fatigue.

Methods: We recruited adult patients from a Neuro-COVID-19 Clinic with persistence of disabling symptoms beyond 6 weeks from acute infection. Self-reported symptoms were assessed with Patient-Reported Outcomes Measurement Information System instruments. We evaluated cognitive performance using NIH Toolbox measures and assessed sleep and rest-activity rhythms by 7 days of wrist actigraphy. We performed level 2 polysomnography in a subset of 20 participants.

Results: We studied 58 participants: 83% White, 59% female and 91% not hospitalized for COVID-19. Fatigue severity was significantly correlated with worse self-reported cognitive abilities but not with objectively measured cognitive performance and with greater depression symptoms, several rest activity rhythm and light exposure disruption measures, and greater actigraphy measured sleep time and time in bed. A multivariable model found significant, independent associations between fatigue severity and subjective cognitive abilities, depression symptoms, and rest-activity rhythm disruption.

Conclusion/Discussion: Long total sleep times, disruption of light exposure and circadian rest-activity patterns, depression and subjective cognitive impairment are associated with PASC fatigue. Behaviorally influenced sleep and circadian abnormalities may exacerbate fatigue and be targets for therapeutic interventions.

Key Topics:

• Clinical assessment and pathogenesis of clinical manifestations