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Abstract Background Post-acute sequelae of SARS-CoV-2 infection (PASC) symptoms have broad impact, and may affect individuals regardless of COVID-19 severity, socioeconomic status, race, ethnicity, or age. A prominent PASC symptom is cognitive dysfunction, colloquially referred to as “brain fog” and characterized by declines in short-term memory, attention, and concentration. Cognitive dysfunction can severely impair quality of life by impairing daily functional skills and preventing timely return to work. Methods RECOVER-NEURO is a prospective, multi-center, multi-arm, phase 2, randomized, active-comparator design investigating 3 interventions: (1) BrainHQ is an interactive, online cognitive training program; (2) PASC-Cognitive Recovery is a cognitive rehabilitation program specifically designed to target frequently reported challenges among individuals with brain fog; (3) transcranial direct current stimulation (tDCS) is a noninvasive form of mild electrical brain stimulation. The interventions will be combined to establish 5 arms: (1) BrainHQ; (2) BrainHQ + PASC-Cognitive Recovery; (3) BrainHQ + tDCS-active; (4) BrainHQ + tDCS-sham; and (5) Active Comparator. The interventions will occur for 10 weeks. Assessments will be completed at baseline and at the end of intervention and will include cognitive testing and patient-reported surveys. All study activities can be delivered in Spanish and English. Discussion This study is designed to test whether cognitive dysfunction symptoms can be alleviated by the use of pragmatic and established interventions with different mechanisms of action and with prior evidence of improving cognitive function in patients with neurocognitive disorder. If successful, results will provide beneficial treatments for PASC-related cognitive dysfunction. Trial registration ClinicalTrials.gov NCT05965739. Registered on July 25, 2023.

BackgroundAn ongoing global challenge is managing brain health and understanding how performance changes across the lifespan. ObjectiveWe developed and deployed a set of self-administrable, computerized assessments designed to measure key indexes of brain health across the visual and auditory sensory modalities. In this pilot study, we evaluated the usability, feasibility, and performance distributions of the assessments in a home-based, real-world setting without supervision. MethodsPotential participants were untrained users who self-registered on an existing brain training app called BrainHQ. Participants were contacted via a recruitment email and registered remotely to complete a demographics questionnaire and 29 unique assessments on their personal devices. We examined participant engagement, descriptive and psychometric properties of the assessments, associations between performance and self-reported demographic variables, cognitive profiles, and factor loadings. ResultsOf the 365,782 potential participants contacted via a recruitment email, 414 (0.11%) registered, of whom 367 (88.6%) completed at least one assessment and 104 (25.1%) completed all 29 assessments. Registered participants were, on average, aged 63.6 (SD 14.8; range 13-107) years, mostly female (265/414, 64%), educated (329/414, 79.5% with a degree), and White (349/414, 84.3% White and 48/414, 11.6% people of color). A total of 72% (21/29) of the assessments showed no ceiling or floor effects or had easily modifiable score bounds to eliminate these effects. When correlating performance with self-reported demographic variables, 72% (21/29) of the assessments were sensitive to age, 72% (21/29) of the assessments were insensitive to gender, 93% (27/29) of the assessments were insensitive to race and ethnicity, and 93% (27/29) of the assessments were insensitive to education-based differences. Assessments were brief, with a mean duration of 3 (SD 1.0) minutes per task. The pattern of performance across the assessments revealed distinctive cognitive profiles and loaded onto 4 independent factors. ConclusionsThe assessments were both usable and feasible and warrant a full normative study. A digital toolbox of scalable and self-administrable assessments that can evaluate brain health at a glance (and longitudinally) may lead to novel future applications across clinical trials, diagnostics, and performance optimization.