Long COVID Brain Fog Treatment: Findings from a Pilot Randomized Controlled Trial of Constraint-Induced Cognitive Therapy
Authors: Uswatte Gitendra , Taub Edward , Ball Karlene , Mitchell Brandon S. , Blake Jason A. , McKay Staci , Biney Fedora , Iosipchuk Olesya , Hempfling Piper , Harris Elise , Dickerson Anne , Lokken Kristine , Knight Amy J. , Mark Victor W. , Agnihotri Shruti , Cutter Gary 
Published: July 2024

Purpose

Long COVID brain fog is often disabling. Yet, no empirically-supported treatments exist. This study’s objectives were to evaluate feasibility and efficacy, provisionally, of a new rehabilitation approach, Constraint-Induced Cognitive Therapy (CICT), for post-COVID-19 cognitive sequelae.

Design

Sixteen community-residents ≥ 3-months post-COVID-19 infection with mild cognitive impairment and dysfunction in instrumental activities of daily living (IADL) were enrolled. Participants were randomized to Immediate-CICT or treatment-as-usual (TAU) with crossover to CICT. CICT combined behavior change techniques modified from Constraint-Induced Movement Therapy with Speed of Processing Training, a computerized cognitive-training program. CICT was deemed feasible if (a) ≥80% of participants completed treatment, (b) the same found treatment highly satisfying and at most moderately difficult, and (c) <2 study-related, serious adverse-events occurred. The primary outcome was IADL performance in daily life (Canadian Occupational Performance Measure). Employment status and brain fog (Mental Clutter Scale) were also assessed.

Results

Fourteen completed Immediate-CICT (n=7) or TAU (n=7); two withdrew from TAU before their second testing session. Completers were [M(SD)]: 10 (7) months post-COVID; 51 (13) years old; 10 females, 4 males; 1 African American, 13 European American. All the feasibility benchmarks were met. Immediate-CICT, relative to TAU, produced very large improvements in IADL performance (M=3.7 points, p<.001,d=2.6) and brain fog (M=−4 points, p<.001,d=−2.9). Four of five non-retired Immediate-CICT participants returned-to-work post-treatment; no TAU participants did,p=.048.

Conclusions

CICT has promise for reducing brain fog, improving IADL, and promoting returning-to-work in adults with Long COVID. Findings warrant a large-scale RCT with an active-comparison group.

IMPACT

Brain fog in adults with Long COVID is often associated with dysfunction in everyday activities and unemployment. Yet, there are no empirically supported treatments targeting cognition in this population. Findings from this small-scale, pilot randomized controlled trial (RCT) suggest that a novel intervention, i.e., Constraint-Induced Cognitive Therapy, is a feasible cognitive rehabilitation method in adults with Long COVID cognitive sequelae with promise of (a) improving performance of cognition-based tasks in daily life and (b) promoting return-to-work. Further studies with larger sample sizes are warranted.

Speed of Processing Training (SOPT) has been shown to increase processing speed in older adults without neurological disorders but has not been applied to adults with brain fog due to Long COVID, in whom slowing of cognitive processing speed is common. The results of this pilot RCT suggest that SOPT, in conjunction with behavior change techniques, may increase cognitive processing speed in this brain-injured population.