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RECOVER-NEURO: Study protocol for a multi-center, multi-arm, phase 2, randomized, active comparator trial evaluating three interventions for cognitive dysfunction in post-acute sequelae of SARS-CoV-2 infection (PASC)

Knopman, DS; Laskowitz, DT; Koltai, DC; et al., Trials

View Full Publication on PubMed


May 2024




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: NCT05965739. Registered on July 25, 2023. 


David S Knopman, Daniel T Laskowitz, Deborah C Koltai, Leigh E Charvet, Jacqueline H Becker, Alex D Federman, Juan Wisnivesky, Henry Mahncke, Thomas M Van Vleet, Lucinda Bateman, Dong-Yun Kim, Ashley O'Steen, Melissa James, Adam Silverstein, Yuliya Lokhnygina, Jennifer Rich, Bryan J Feger, Kanecia O Zimmerman


Cognitive dysfunction; Cognitive rehabilitation; Cognitive training; Long-COVID; Post-acute sequelae of SARS-CoV-2 infection; Transcranial direct current stimulation; tDCS

Short Summary

The researchers and study team running the RECOVER-NEURO clinical trial published a paper detailing the study’s design. RECOVER-NEURO is looking at 3 possible treatments for cognitive dysfunction, or brain fog, symptoms related to Long COVID. The possible treatments, also called study interventions, are BrainHQ (an interactive online brain training program), PASC-Cognitive Recovery (an online goal management training program), and transcranial direct current stimulation (a safe, noninvasive form of brain stimulation). The research team is using a variety of assessments, including brain function tests and participant surveys, to determine if these study interventions reduce brain fog symptoms and help people function better.

People with brain fog may have trouble thinking clearly, remembering things, or focusing on tasks, which can severely affect their daily functioning and quality of life. Results from this study will help the Long COVID community learn if BrainHQ, PASC-Cognitive Recovery, and transcranial direct current stimulation can be used to treat cognitive dysfunction symptoms related to Long COVID.



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