Trajectories of Neurologic Recovery 12 Months After Hospitalization for COVID-19: A Prospective Longitudinal Study

Abstract

Background and objective: Little is known about trajectories of recovery 12 months after hospitalization for severe COVID-19.

Methods: We conducted a prospective, longitudinal cohort study of patients with and without neurologic complications during index hospitalization for COVID-19 from March 10, 2020, to May 20, 2020. Phone follow-up batteries were performed at 6 and 12 months after COVID-19 onset. The primary 12-month outcome was the modified Rankin Scale (mRS) score comparing patients with or without neurologic complications using multivariable ordinal analysis. Secondary outcomes included activities of daily living (Barthel Index), telephone Montreal Cognitive Assessment (t-MoCA), and Quality of Life in Neurologic Disorders (Neuro-QoL) batteries for anxiety, depression, fatigue, and sleep. Changes in outcome scores from 6 to 12 months were compared using nonparametric paired-samples sign test.

Results: Twelve-month follow-up was completed in 242 patients (median age 65 years, 64% male, 34% intubated during hospitalization) and 174 completed both 6- and 12-month follow-up. At 12 months, 197/227 (87%) had ≥1 abnormal metric: mRS >0 (75%), Barthel Index <100 (64%), t-MoCA ≤18 (50%), high anxiety (7%), depression (4%), fatigue (9%), or poor sleep (10%). Twelve-month mRS scores did not differ significantly among those with (n = 113) or without (n = 129) neurologic complications during hospitalization after adjusting for age, sex, race, pre-COVID-19 mRS, and intubation status (adjusted OR 1.4, 95% CI 0.8-2.5), although those with neurologic complications had higher fatigue scores (T score 47 vs 44; p = 0.037). Significant improvements in outcome trajectories from 6 to 12 months were observed in t-MoCA scores (56% improved, median difference 1 point; p = 0.002) and Neuro-QoL anxiety scores (45% improved; p = 0.003). Nonsignificant improvements occurred in fatigue, sleep, and depression scores in 48%, 48%, and 38% of patients, respectively. Barthel Index and mRS scores remained unchanged between 6 and 12 months in >50% of patients.

Discussion: At 12 months after hospitalization for severe COVID-19, 87% of patients had ongoing abnormalities in functional, cognitive, or Neuro-QoL metrics and abnormal cognition persisted in 50% of patients without a history of dementia/cognitive abnormality. Only fatigue severity differed significantly between patients with or without neurologic complications during index hospitalization. However, significant improvements in cognitive (t-MoCA) and anxiety (Neuro-QoL) scores occurred in 56% and 45% of patients, respectively, between 6 and 12 months. These results may not be generalizable to those with mild or moderate COVID-19.

Figure 1. Study Enrollment

Enrollment flow chart identifying inclusion and exclusion of patients with or without neurologic complications from index COVID-19 hospitalization to 6-month and 12-month follow-up. A total of 395 COVID-19 patients with neurologic complications who survived index hospitalization were propensity score matched by age, sex, and intubation status to 395 patients with COVID-19 hospitalized during the same time frame and without neurologic complications who survived to discharge.

Figure 2. Ordinal Analysis of 12-Month mRS Scores

Modified Rankin Scale (mRS) scores 12 months after COVID-19 symptom onset in patients with and without neurologic complications during index COVID-19 hospitalization. There was no significant difference between groups in mRS scores using multivariable ordinal logistic regression analysis adjusting for age, sex, race, pre–COVID-19 mRS, and intubation status (adjusted odds ratio for worse mRS scores 1.4, 95% CI 0.8–2.5; p = 0.258). mRS 0 = no symptoms or disability; 1 = symptoms, but no disability; 2 = slight disability, unable to carry out all previous activities, but able to function without assistance; 3 = moderate disability, requiring help, but able to walk without assistance; 4 = moderately severe disability, unable to walk or attend to bodily needs without assistance; 5 = severe disability, bedbound, incontinent, requiring constant care; 6 = dead.

Figure 3. Percentage of Patients With Improved, Worse, or Same Outcome Scores Between 6 and 12 Months After COVID-19 Hospitalization (N = 174)

mRS = modified Rankin Scale; t-MoCA = telephone Montreal Cognitive Assessment.