What is the treatment approach for post-COVID-19 (coronavirus disease 2019) brain fog in patients with impaired cognitive function?

Treatment of Post-COVID Brain Fog

Begin with cognitive rehabilitation as first-line therapy, specifically Constraint-Induced Cognitive Therapy (CICT) combined with computerized cognitive training, which produces very large improvements in brain fog and daily functioning. 1

Initial Assessment and Recognition

• Conduct objective cognitive testing rather than relying solely on patient self-report, as some patients may not recognize or report their impairment 2
• Recognize that cognitive impairment affects approximately 22% of patients at 12 weeks post-infection and may increase to 26% at 12 months, persisting for at least 2 years 2
• Do not attribute cognitive symptoms solely to anxiety or depression—cognitive impairment is independent of these conditions and requires specific treatment 2
• Understand that cognitive deficits occur regardless of initial COVID-19 severity, affecting both hospitalized and non-hospitalized patients 2

First-Line Treatment: Cognitive Rehabilitation

Implement Constraint-Induced Cognitive Therapy (CICT), which combines behavior change techniques with Speed of Processing Training (computerized cognitive training program). 1

• CICT produces mean improvements of 3.7 points in instrumental activities of daily living (IADL) performance (effect size d=2.6) and 4-point reductions in brain fog severity (effect size d=-2.9) 1
• This intervention enabled 80% of non-retired participants to return to work post-treatment compared to 0% in treatment-as-usual groups 1
• Treatment adherence exceeds 80% with high patient satisfaction and minimal difficulty 1

Alternative cognitive rehabilitation approach: Multidisciplinary rehabilitation enhanced with individualized neuropsychological treatment (45 minutes daily). 3

• This produces significant improvements in MoCA scores (20.4 to 24.7 points, p<0.0001) over approximately 30 days 3
• Specific cognitive domains that improve include attention, abstract reasoning, language repetition, memory recall, orientation, and visuospatial abilities 3
• 43% of patients with cognitive impairment normalize their cognitive function after this intervention 3

Adjunctive Non-Pharmacological Interventions

Implement breathing techniques and mind-body practices for concurrent symptom management:

• Breath relaxation training and mindfulness training for mild psychological symptoms 4, 5
• Tai Chi exercises, which improve multiple aspects of post-COVID recovery including cognitive symptoms 4, 5
• Olfactory training for patients with smell/taste disturbances, which can be associated with cognitive issues 2

Pharmacological Considerations

Currently, no medications have proven efficacy specifically for post-COVID cognitive impairment. 2

However, bupropion extended-release may be considered for refractory cases based on case series evidence:

• Bupropion (dopamine and norepinephrine reuptake inhibitor) produced dramatic recovery in patients with persistent brain fog, memory impairment, mental exhaustion, and inattention 6
• Proposed mechanisms include blocking hippocampal cell loss, increasing neural activity in the cingulate cortex, and decreasing proinflammatory cytokines 6
• Dosing and time to resolution vary by individual 6

Theoretical candidates under investigation include luteolin, cannabidiol, cannabivarine, methylene blue, and clomipramine, but these lack clinical evidence. 2

Addressing Modifiable Contributing Factors

Systematically address sleep disturbances and fatigue, which exacerbate cognitive symptoms: 2

• Treat underlying sleep disorders that may worsen cognitive function
• Manage fatigue through pacing strategies and energy conservation

Provide psychological support for concurrent mood symptoms (present in >60% of patients): 4

• For mild symptoms: psychological self-adjustment, breath relaxation, mindfulness training 4
• For moderate to severe symptoms: combine medication with psychotherapy, implement cognitive behavioral therapy, psychological first aid, and stress management 4
• Use medications with short half-life and low drug-drug interaction risk at lowest effective doses for shortest duration 4

Monitoring and Follow-Up

• Monitor for progression or worsening of symptoms over time, as cognitive impairment may increase rather than resolve spontaneously 2
• Continue mental health and psychosocial support with regular follow-up to ensure symptom improvement 4
• Establish dynamic evaluation and warning mechanisms for prompt identification and intervention 4

Brain Imaging

Do not routinely order brain imaging for post-COVID cognitive complaints except to rule out other causes (stroke, mass lesions, etc.). 2

• Hypometabolism findings on imaging are primarily for research purposes and do not guide clinical management 2

Clinical Trial Enrollment

• Consider enrollment in clinical trials of investigational therapies given the limited proven treatment options 2

Critical Pitfalls to Avoid

• Never dismiss cognitive symptoms as "just anxiety" or "just depression"—these are distinct, independent conditions requiring specific cognitive rehabilitation 2
• Never assume symptoms will spontaneously resolve—cognitive impairment persists or worsens over time in many patients, unlike anxiety and depression 2
• Never delay cognitive rehabilitation while waiting for pharmacological solutions—rehabilitation has the strongest evidence for efficacy 1, 3