Cognitive Rehabilitation and Functional Outcomes in Long COVID-Related Cognitive Impairment: A Randomized Clinical Trial

Importance: Cognitive impairment is common in long COVID and severely affects daily life, with no proven treatments to date. Objective: To evaluate the ability of cognitive rehabilitation (CR) to improve goal attainment, cognitive, and clinical outcomes in individuals with cognitive impairment as part of long COVID. Design, Setting, and Participants: This multicenter, single-blind, 2-arm, parallel-group randomized clinical trial was conducted at 3 sites in England between February 2023 and March 2024. Participants were adults aged 30 to 60 years with prior COVID-19 infection and objective cognitive impairment (≥1 SD below age norm in ≥2 cognitive domains). A sample size of 88 participants (44:44) was required to detect a conservative effect of 0.7 on the goal attainment score at 3 months. Interventions: Participants were randomized (1:1) to CR or treatment as usual (TAU). CR consisted of 10 individual 1-hour sessions conducted once per week with a trained researcher, applying evidence-based strategies to 3 individually selected, personally meaningful functional goals. TAU was variable, with most participants having access to specialist memory clinics. Main Outcome and Measures: The primary outcome consisted of participant-reported goal-attainment scores at 3 months after randomization measured by the Bangor Goal-Setting Interview. Analysis was conducted on an intention-to-treat basis using multilevel mixed-effects models with 2-sided 95% CIs and 5% significance. Results: A total of 78 participants (24 male [30.8%] and 54 female [69.2%]; mean [SD] age, 47.3 [7.2] years) were randomized, including 38 individuals in CR and 40 individuals in TAU groups. At 3 months after randomization, goal attainment was significantly greater in the CR compared with the TAU group (adjusted mean difference, 2.88 [95% CI, 2.03-3.73]; P < .001; Cohen d = 1.57), with CR providing a large and clinically meaningful treatment effect. This was sustained at 6 months, with a lower effect size (adjusted mean difference, 1.72 [95% CI, 0.86-2.57]; P < .001; Cohen d = 0.91). Conclusions and relevance: In this study, individualized, goal-oriented CR led to significant and sustained improvements in goal attainment in people with long COVID-related cognitive impairment. These findings may guide and inform the provision of CR treatments and services for people living with long COVID. Trial Registration: ClinicalTrials.gov Identifier: NCT05731570.