Research Article: Longitudinal trajectories of neurologic symptoms and cognitive associations at 36-months post-hospitalization for COVID-19
Abstract:
A substantial proportion of individuals hospitalized for COVID 19 experience persistent neurological and psychiatric symptoms. The long-term trajectories of these symptoms, collectively referred to as neuropsychiatric manifestation of Post-Acute Sequelae of COVID-19 (Neuro-PASC), and their association with cognitive outcomes remains poorly understood. We conducted a 36-month longitudinal cohort study to characterize Neuro-PASC symptom trajectories, examine their associations with domain specific cognitive performance, and identify baseline biological predictors of long-term neurological outcomes.
We performed a longitudinal observational study of 227 adults ages 19–79 (mean?=?47.6), previously hospitalized for COVID-19 symptoms. Participants completed follow-up assessments at 3/6-, 12-, 24-, and 36-months post-hospitalization. At each visit, structured, self-reported neurological symptom surveys, digital cognitive testing (BrainCheck), and updated medical history were collected. Generalized estimating equation models assessed longitudinal associations between cognitive subdomains and individual symptoms. K-means clustering identified distinct symptom trajectory groups. Baseline demographic and clinical factors were examined and compared across symptom trajectory groups.
Several neurological symptoms increased in prevalence over 36?months following hospitalization in some individuals. Fatigue remained most common (53–65%), followed by memory/concentration difficulties (47–61%) and sleep disturbances (40–48%). Dizziness had a modest increase (30–49%), while coordination impairment more than doubled (18–41%). Headaches remained prevalent and relatively stable (21–35%). Symptom co-occurrence strengthened over time, with fatigue frequently clustering with other symptoms (up to 45% at 36?months). Overall BrainCheck composite scores were not independently associated with neurological symptoms, but significant associations emerged for executive function, memory, and attention, including time-dependent effects. Trajectory analyses identified distinct longitudinal patterns (1. stable trajectory, 2. worsening trajectory, and 3. improving trajectory), associated with baseline demographics, comorbidities, and acute disease severity.
Neurological symptoms can persist or worsen up to 36?months post- COVID-19 hospitalization, even as some cognitive functions show partial recover. Distinct symptom trajectories and evolving associations with specific cognitive domains and biological outcomes underscore the heterogeneous and dynamic nature of Neuro-PASC, supporting the need for long-term neuropsychological monitoring and informing targeted interventions and mechanistic studies.
Introduction:
A substantial proportion of individuals hospitalized for COVID 19 experience persistent neurological and psychiatric symptoms. The long-term trajectories of these symptoms, collectively referred to as neuropsychiatric manifestation of Post-Acute Sequelae of COVID-19 (Neuro-PASC), and their association with cognitive outcomes remains poorly understood. We conducted a 36-month longitudinal cohort study to characterize Neuro-PASC symptom trajectories, examine their associations with domain specific cognitive…
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