San Francisco, May 5, 2025 — In a groundbreaking advancement poised to redefine treatment paradigms for Long COVID, researchers at the University of Alabama at Birmingham (UAB) have conducted what is believed to be the first randomized controlled trial revealing substantial, even transformative improvements in the complex constellation of symptoms plaguing Long COVID sufferers. Long COVID, characterized by persistent cognitive deficits, fatigue, and neurological dysfunction months following initial SARS-CoV-2 infection, has baffled the medical community due to its multifaceted pathology and elusive treatment options. The UAB investigation leveraged a novel intervention combining progressive computerized brain exercises with an adaptive coaching model aimed at harnessing neuroplasticity—the brain’s enduring capacity for change—to remediate cognitive and functional impairments.
The core technological platform employed was BrainHQ, a commercially available brain exercise app developed by Posit Science, renowned for its evidence-based, neuroscience-driven cognitive training programs. These programs utilize adaptive algorithms that continuously calibrate task difficulty, stimulating targeted neural circuits to promote synaptic strengthening and cortical reorganization. By pushing cognitive boundaries through progressively challenging exercises, the intervention intensifies neuroplastic mechanisms that undergird recovery processes. Notably, this approach contrasts with traditional passive or pharmacologic treatments by actively engaging patients in tailored mental workouts that translate into meaningful real-world functional gains.
Long COVID’s burden in the United States alone is staggering, with estimates suggesting approximately 20 million individuals have been diagnosed and 9 to 10 million still experiencing lingering symptoms. A significant subset, roughly 14%, remain unable to resume their occupational roles even three months following initial infection, underscoring the urgent need for evidence-based rehabilitative strategies. The UAB study enrolled 16 community-dwelling adults, all more than three months post-COVID infection and exhibiting mild cognitive impairment alongside difficulties in managing instrumental activities of daily living. Participants were randomized into either the intervention group receiving BrainHQ exercises coupled with coaching or a wait-list control group, ensuring rigorous scientific evaluation.
Results from this early-phase trial were striking, with the intervention cohort demonstrating statistically significant and notably large improvements in key outcome measures related to cognitive performance and daily activity satisfaction. Secondary measures bore equally encouraging findings, highlighting substantial reductions in depression, fatigue, and the hallmark “brain fog” associated with Long COVID. Moreover, participants exhibited enhanced brain processing speeds, an objective neurocognitive marker often diminished in post-viral syndromes. While global cognition metrics did not shift significantly, the targeted effects on specific cognitive domains and symptom clusters represent a meaningful therapeutic advance.
Perhaps most remarkable was the functional impact observed: 80% of the active working-age participants in the intervention arm successfully returned to their jobs, a stark contrast to the control group where no such return was reported. This real-world outcome solidifies the potential of neuroplasticity-centered interventions to restore not only cognitive faculties but also vocational capacity, a critical determinant of quality of life and socioeconomic wellbeing. The robust coaching component, inspired by constraint-induced movement therapy principles, provided motivational scaffolding and fostered sustained engagement with the challenging training regimen, possibly amplifying the neuroplastic effects.
The scientific underpinnings of this intervention are deeply rooted in decades of neuroplasticity research, with foundational contributions from Dr. Michael Merzenich, whose seminal work demonstrated that adult brains retain the capacity for profound chemical, structural, and functional remodeling throughout life. Dr. Merzenich’s pioneering insights, which catalyzed the development of cochlear implants, have since evolved toward designing computerized exercises that simulate the brain’s natural learning processes. His role as co-founder and chief scientific officer of Posit Science ensures that cutting-edge neuroscience informs BrainHQ’s evolving exercise protocols.
At UAB, further refinement of neuroplasticity-based rehabilitation has been driven by the work of Dr. Karlene Ball and Dr. Edward Taub. Dr. Ball’s efforts elucidated the potential of plasticity-oriented exercises to mitigate age-related cognitive decline, while Dr. Taub’s development of constraint-induced movement therapy revolutionized rehabilitation approaches to movement disorders by compelling use-dependent cortical reorganization. Their expertise informed the coaching methodology integrated into this study, which supported progressive challenge and incremental mastery—key elements known to potentiate durable neural adaptation.
Prior applications of BrainHQ exercises in populations including older adults and patients with various chronic illness states—such as cancer, heart failure, multiple sclerosis, schizophrenia, and mild cognitive impairment—have documented cognitive and functional gains, including improvements in depressive symptoms, fatigue, and employment status. However, the magnitude of improvements realized in this Long COVID cohort surpasses many earlier findings, potentially attributable to the greater baseline impairment and the synergistic effect of combining brain exercise with targeted coaching. This combination may represent a critical innovation in neurorehabilitation strategies.
From a mechanistic perspective, intensive, repetitive, and progressively challenging cognitive tasks are postulated to drive synaptic strengthening via long-term potentiation, augment myelination, and promote neurogenesis in hippocampal and prefrontal circuits. Such neurophysiological adaptations could counteract the neuroinflammatory and microvascular insults hypothesized to underlie Long COVID cognitive dysfunction. Enhancing processing speed likely reflects improvements in white matter integrity and neural network efficiency, foundational to higher-order executive function and daily task performance.
Dr. Henry Mahncke, CEO of Posit Science, underscored the promise of brain training as a non-pharmacologic intervention, stating that the observed benefits may herald a turning point in Long COVID management. Given the substantial unmet clinical need, scalable digital therapeutics like BrainHQ offer an accessible, cost-effective, and patient-empowering avenue for rehabilitation, suitable for deployment across diverse healthcare settings.
The study’s modest sample size and primary focus on feasibility highlight the necessity for expanded trials to confirm efficacy and explore long-term outcomes. Nonetheless, these initial findings inject critical optimism into a field marked by diagnostic ambiguity and therapeutic inertia. Future research directions include elucidating neurobiological correlates of response via neuroimaging, optimizing cognitive exercise protocols for personalized intervention, and investigating combinatorial approaches integrating cognitive training with pharmacotherapies or physical rehabilitation.
BrainHQ’s extensive validation across over 300 peer-reviewed studies substantiates its broad applicability and underscores its potential as a foundational tool in cognitive health. The platform’s adoption by Medicare Advantage plans, academic medical centers, and peak performance organizations attests to its versatility and clinical relevance. Individuals can access a free daily exercise via the platform’s website, democratizing cognitive health resources.
In summary, this pioneering controlled trial signifies a major step forward in Long COVID treatment, illustrating that harnessing neuroplasticity through structured brain exercises and coaching not only ameliorates debilitating cognitive symptoms but also restores individuals’ ability to engage meaningfully in daily life and work. As Long COVID continues to impose a heavy societal toll, tech-enabled neurorehabilitation may emerge as a pivotal element in comprehensive recovery paradigms.
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Subject of Research: People
Article Title: Long COVID brain fog treatment: An early-phase randomized controlled trial of constraint-induced cognitive therapy signals go.
News Publication Date: May 5, 2025
Web References:
– https://psycnet.apa.org/doiLanding?doi=10.1037%2Frep0000626
– https://www.brainhq.com/
– https://www.cidrap.umn.edu/covid-19/about-8-us-adults-have-ever-had-long-covid-survey-finds
– https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0300947
– http://dx.doi.org/10.1037/rep0000626
– https://www.brainhq.com/world-class-science/science-team-research-partners/dr-michael-merzenich-phd/
– https://www.uab.edu/cas/psychology/people/faculty/karlene-k-ball
– https://www.uab.edu/cas/psychology/people/emeritus-faculty/edward-taub
– https://www.brainhq.com/world-class-science/information-researchers/
– https://www.brainhq.com/world-class-science/the-proven-benefits-of-brainhq
References: 10.1037/rep0000626 (Rehabilitation Psychology Journal Article)
Keywords: Health and medicine, Diseases and disorders, Health care, Human health, Medical cybernetics
