Cognitive Rehabilitation in Post-COVID-19 Condition (TRAINCOVID)

Cognitive Rehabilitation in Post-COVID-19 Condition: A Study Protocol for a Randomized Controlled Trial

University of Oslo, Icahn School of Medicine at Mount Sinai, University of Toronto, UiT The Arctic University of Norway, Oslo University Hospital

Post-COVID-19 condition is frequently comprised of persistent cognitive sequela, including deficits in attention and executive functions (EFs). Goal Management Training (GMT) is a cognitive rehabilitation (CR) intervention for improving attention and EFs that has received empirical support in studies of other patient groups. The present study aims to determine the efficacy of GMT for improving everyday attention and EFs in adults who experience persistent cognitive deficits after COVID-19. The study is a randomized controlled trial (RCT), comparing the efficacy of GMT to a wait list control condition (WL), for improving persistent cognitive sequela in post-COVID-19 condition. The study aims to recruit 240 participants aged 18 to 65 years with a history of laboratory- or home-test confirmed, SARS-CoV-2 infection (> 3 months since infection) and perceived attentional and EF difficulties in daily life that have lasted for at least two months and that cannot be explained by an alternative diagnosis. Participants will be randomized to either group-based GMT (n = 120) or WL (n = 120). GMT will be internet-delivered to groups of six participants in six two-hour sessions delivered weekly (five weeks). The primary outcome will be the Metacognition Index of the Behavior Rating Inventory of Executive Function - Adult Version, a self-report measure assessing everyday EF difficulties, at six months post-treatment. Secondary outcomes include performance-based neurocognitive measures and rating scales of cognition, emotional health, quality of life, and fatigue. Secondary aims include to explore to what extent potential early change predicts outcome, and to examine what characterize those who profit from GMT, in addition to describe the neurocognitive and emotional health in a Covid-19 sample. The investigators will also examine potential effects of GMT at 2- and 5-year follow-up.

Internet-delivered group-based GMT to groups of six participants in six two-hour sessions delivered weekly (five weeks). Manualized intervention.

Goal Management Training is a cognitive rehabilitation intervention that relies on metacognitive strategies to reengage top-down attention processes, in addition to teaching problem-solving techniques, attempting to address executive dysfunctions.

The Metacognition Index from the Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A)

Self-report measure of daily life executive function (metacognition). Range:70-210. Higher score indicate greater executive dysfunction.

The Behaviour regulation Index from Behavior Rating Inventory of Executive Function - Adult Version (BRIEF-A)

Self-report measure of daily life executive function (behaviour regulation). Range: 70-210. Higher score indicate greater executive dysfunction.

Cambridge Neuropsychological Test Automated Battery (CANTAB), subtests: the Stop Signal Task, Spatial Working Memory, Intra-Extra Dimensional Set Shift and Rapid Visual Information Processing

Self-report measure of symptoms of anxiety and depression. The maximum score is 21 for depression and 21 for anxiety, range 0-21 on each scale. A higher score = more symptoms.

Self-report measure of daily-life cognitive difficulties. The total score range from 0 to 80, with a higher score indicating greater perceived cognitive impairment.

Self-report measure of daily-life cognitive difficulties. The total score range from 0 to 52, with a higher score indicating greater perceived cognitive impairment.

Self-report measure of quality of life. Range 0-10; a high score defines a more favorable health state.

Self-report measure of quality of life. The range of the EQ-5D index scores is 0 to 1 (1 indicates the best health state), but negative scores as low as-0.59 are possible for health states deemed to be worse than death.

Self-report measure of social support. 8 items. The total score range from 8 to 40. Higher score indicates more social support.

Self-report measure of fatigue symptoms. 14 items. The total score range from 0 to 56 for both frequency and severity for each item.

Inclusion Criteria: history of laboratory- or home-test confirmed, SARS-CoV-2 infection (> 3 months since infection) perceived cognitive difficulties (attention, memory, EF) affecting everyday functioning that have lasted for at least two months and that cannot be explained by an alternative diagnosis age between 18-65 years Exclusion Criteria: ongoing alcohol- or substance abuse, premorbid insult and/or comorbid neurological disease, severe neurocognitive problems interfering with the capacity to participate, sensory disorders biasing cognitive assessment, psychotic disorders, lack of proficiency in Norwegian, and being previously enrolled in a GMT trial.

Hagen BI, Lerdal A, Soraas A, Landro NI, Bo R, Smastuen MC, Becker J, Stubberud J. Cognitive rehabilitation in post-COVID-19 condition: A study protocol for a randomized controlled trial. Contemp Clin Trials. 2022 Nov;122:106955. doi: 10.1016/j.cct.2022.106955. Epub 2022 Oct 5.