Transcranial Direct Current Stimulation for Long COVID Brain Fog and Fatigue (NEUROSTIM-LC)

The Impact of Transcranial Direct Current Stimulation on Quality of Life, Brain Fog, and Fatigue in Patients With Long COVID: Study Protocol of the NEUROSTIM-LC Study

Long COVID can cause persistent symptoms such as fatigue, cognitive difficulties commonly described as brain fog, reduced exercise tolerance, and impaired quality of life. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that may help modulate brain activity in regions involved in cognition, fatigue, and executive function.

The NEUROSTIM-LC study will evaluate the feasibility and potential effects of repeated tDCS sessions in adults with long COVID presenting fatigue and/or brain fog. Participants will receive 30 sessions of tDCS applied over the left dorsolateral prefrontal cortex. Assessments will be performed before and after the intervention to evaluate changes in quality of life, fatigue, cognitive function, brain metabolism, physical performance, autonomic function, sleep quality, psychological symptoms, respiratory function, and blood biomarkers.

Study Overview

• Status: Not yet recruiting
• Conditions: Fatigue; Cognitive Dysfunction; Long COVID; Post-COVID Conditions
• Intervention / Treatment: Device: Transcranial Direct Current Stimulation

Detailed Description

The NEUROSTIM-LC study is a prospective, single-arm, interventional before-and-after study designed to evaluate the feasibility, tolerability, and preliminary effects of transcranial direct current stimulation (tDCS) in patients with long COVID. The study will recruit adults aged 18 to 70 years diagnosed with long COVID according to World Health Organization criteria and presenting persistent fatigue and/or cognitive impairment commonly described as brain fog.

Participants will receive 30 sessions of tDCS delivered over consecutive weeks in a controlled clinical setting. Stimulation will be applied over the left dorsolateral prefrontal cortex, with the anode positioned at F3 according to the international 10-20 EEG system and the cathode over the contralateral supraorbital region. Each session will be delivered at 2 mA for 20 minutes. Sessions will be performed on weekdays under the supervision of trained healthcare professionals, and adherence, tolerability, and adverse effects will be monitored throughout the intervention period.

Assessments will be conducted at baseline and after completion of the intervention. Clinical outcomes will include health-related quality of life, fatigue, cognitive performance, sleep quality, anxiety and depression symptoms, and perceived symptom evolution. Neurobiological and physiological outcomes will include brain metabolism assessed by PET-CT, autonomic nervous system activity assessed by heart rate variability, exercise capacity assessed using the Ekblom-Bak submaximal cycle ergometer test, upper-limb muscle strength assessed by handgrip dynamometry, lower-limb neuromuscular performance assessed by countermovement jump testing, respiratory function, oxygen saturation, and routine blood biomarkers. Blood samples may also be stored for future analysis of inflammatory and oxidative stress markers.

The study aims to provide preliminary information on whether repeated tDCS may be associated with measurable improvements in fatigue, brain fog, quality of life, and physiological function in patients with long COVID. The findings will help inform the design of future controlled trials evaluating non-invasive neuromodulation strategies for persistent neurological and fatigue-related symptoms after COVID-19.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Juan Francisco Vigueras, MD; Phone Number: +34 606 63 86 98; Email: juanfraviguerasperez@yahoo.es
• Study Contact Backup: Name: David Morales Álamo, PhD; Phone Number: +34 623 062 814; Email: david.moralesalamo@ulpgc.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adults aged between 18 and 70 years.
• Diagnosis of long COVID according to World Health Organization criteria, defined as symptoms persisting for at least three months after acute SARS-CoV-2 infection and lasting for a minimum of two months without an alternative explanation.
• Presence of persistent fatigue and/or cognitive impairment, commonly described as brain fog, attributed to long COVID and confirmed at screening.
• Stable clinical condition allowing participation in the intervention and assessment procedures.
• Ability to understand the study procedures and provide written informed consent.

Exclusion Criteria:

• Contraindications to transcranial direct current stimulation, including the presence of implanted electronic devices such as pacemakers or neurostimulators, intracranial metallic implants, or history of epilepsy or seizures.
• History of neurological disorders that may affect cognitive function, including stroke, Parkinson's disease, or neurodegenerative disorders.
• Pre-existing conditions associated with chronic fatigue or cognitive impairment prior to SARS-CoV-2 infection, such as fibromyalgia, chronic fatigue syndrome, or multiple sclerosis.
• Severe psychiatric disorders, including psychosis or severe depression.
• Substance abuse, including alcohol or drugs.
• Current oncological treatment with chemotherapy or radiotherapy.
• Pregnancy.
• Any medical condition that, in the opinion of the investigators, may interfere with participation or with the interpretation of the results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: tDCS Intervention; Participants will receive 30 sessions of transcranial direct current stimulation applied over the left dorsolateral prefrontal cortex. Stimulation will be delivered at 2 mA for 20 minutes per session, once daily, five days per week, under supervision of trained healthcare professionals.

Device: Transcranial Direct Current Stimulation; Transcranial direct current stimulation will be delivered using a constant-current stimulator through surface electrodes placed over the scalp. The anode will be positioned over the left dorsolateral prefrontal cortex, corresponding to F3 according to the international 10-20 EEG system, and the cathode will be placed over the contralateral supraorbital region. Each session will be delivered at 2 mA for 20 minutes. Participants will complete 30 sessions.; Other Names: tDCS; Non-invasive brain stimulation; EPTE Bipolar tDCS device

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in EuroQol 5-Dimension 5-Level Questionnaire Score	Health-related quality of life will be assessed using the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L). The EQ-5D-5L assesses five health dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, each rated across five levels of severity. Higher scores or index values reflect better health status, depending on the scoring method used. Changes from baseline to post-intervention will be evaluated.	Baseline and 3 days after completion of the 30-session tDCS intervention
Change in Modified Fatigue Impact Scale Score	Fatigue will be assessed using the Modified Fatigue Impact Scale (MFIS). The MFIS assesses the impact of fatigue on physical, cognitive, and psychosocial functioning. The total score ranges from 0 to 84, with higher scores indicating greater fatigue impact. Changes from baseline to post-intervention will be evaluated.	Baseline and 3 days after completion of the 30-session tDCS intervention
Change in Montreal Cognitive Assessment Score	Global cognitive function will be assessed using the Montreal Cognitive Assessment (MoCA). The MoCA evaluates cognitive domains including attention, memory, language, visuospatial abilities, executive function, abstraction, calculation, and orientation. The total score ranges from 0 to 30, with higher scores indicating better cognitive performance. Changes from baseline to post-intervention will be evaluated.	Baseline and 3 days after completion of the 30-session tDCS intervention
Change in Short Form-36 Health Survey Score	Health-related quality of life will be assessed using the Short Form-36 Health Survey (SF-36). The SF-36 evaluates eight domains of health-related quality of life: physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, and general health. Scores are transformed to a 0-100 scale, with higher scores indicating better health-related quality of life. Changes from baseline to post-intervention will be evaluated.	Baseline and 3 days after completion of the 30-session tDCS intervention
Change in Verbal Fluency Task Performance	Verbal fluency will be assessed using verbal fluency tasks. Performance will be evaluated based on the number of correct words generated within the specified time period. Higher scores indicate better verbal fluency performance. Changes from baseline to post-intervention will be evaluated.	Baseline and 3 days after completion of the 30-session tDCS intervention
Change in Stroop Test Performance	Executive function, inhibitory control, and cognitive flexibility will be assessed using the Stroop test. Performance will be evaluated using test-specific measures such as response accuracy and/or completion time. Better performance is reflected by higher accuracy and/or shorter completion time, depending on the scoring method used. Changes from baseline to post-intervention will be evaluated.	Baseline and 3 days after completion of the 30-session tDCS intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Brain Metabolism	Brain metabolism will be assessed using positron emission tomography-computed tomography (PET-CT). Changes from baseline to post-intervention will be evaluated.	Baseline and 3 days after completion of the 30-session tDCS intervention
Change in Heart Rate Variability	Autonomic nervous system activity will be assessed using heart rate variability (HRV) recorded under resting conditions. Time-domain, frequency-domain, and non-linear HRV indices will be evaluated to characterize changes in autonomic regulation.	Baseline and 3 days after completion of the 30-session tDCS intervention
Change in Endurance Capacity	Endurance capacity will be assessed using the Ekblom-Bak submaximal cycle ergometer test. Heart rate responses, perceived exertion, estimated maximal oxygen uptake, and internal load will be evaluated under standardized conditions.	Baseline and 3 days after completion of the 30-session tDCS intervention
Change in Handgrip Strength	Upper-limb muscle strength will be assessed using handgrip dynamometry. Participants will perform three maximal attempts, and the highest value will be used for analysis.	Baseline and 3 days after completion of the 30-session tDCS intervention
Change in Lower-Limb Neuromuscular Performance	Lower-limb neuromuscular performance will be assessed using the countermovement jump test performed on a force platform. Variables related to force and power production will be evaluated.	Baseline and 3 days after completion of the 30-session tDCS intervention
Tolerability of the tDCS Intervention	Tolerability of the tDCS intervention will be assessed during each stimulation session using session monitoring records and participant reports. Tolerability will be evaluated based on the number of completed tDCS sessions out of the 30 scheduled sessions and the participant's ability to complete each session without clinically relevant discomfort. A higher number of completed sessions indicates greater intervention tolerability	During each tDCS session throughout the 30-session intervention period
Adverse Effects Related to tDCS	Adverse effects related to tDCS will be monitored and recorded at each stimulation session. Potential adverse effects include tingling, itching, headache, discomfort, burning sensation, dizziness, or transient erythema at the electrode site. The presence, type, and severity of adverse effects will be documented. Severity will be classified as mild, moderate, or severe.	During each tDCS session throughout the 30-session intervention period

Collaborators and Investigators

• Sponsor: University of Las Palmas de Gran Canaria
• Collaborators: Canary Islands Health Service; Fundación Canaria Instituto de Investigación Sanitaria de Canarias
• Investigators: Principal Investigator: Juan Francisco Vigueras, MD, Canary Islands Health Service

Study record dates

Study Major Dates

• Study Start (Estimated): September 15, 2026
• Primary Completion (Estimated): December 22, 2027
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: July 11, 2026
• First Submitted That Met QC Criteria: July 11, 2026
• First Posted (Actual): July 16, 2026

Study Record Updates

• Last Update Posted (Actual): July 22, 2026
• Last Update Submitted That Met QC Criteria: July 19, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: tDCS; Neuromodulation; Quality of life; Cognitive impairment; Long COVID; Transcranial direct current stimulation; Heart rate variability; PET-CT; Brain fog; Chronic Fatigue
• Additional Relevant MeSH Terms: Post-Infectious Disorders; COVID-19; Mental Disorders; Pathologic Processes; Chronic Disease; Disease Attributes; Behavioral Symptoms; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Neurocognitive Disorders; Lung Diseases; Cognition Disorders; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Post-Acute COVID-19 Syndrome; Cognitive Dysfunction; Fatigue; Mental Fatigue; Therapeutics; Behavioral Disciplines and Activities; Electric Stimulation Therapy; Convulsive Therapy; Psychiatric Somatic Therapies; Electroshock; Psychological Techniques; Transcranial Direct Current Stimulation
• Other Study ID Numbers: NEUROSTIM-LC-2026; CGC-2025-10415 (Other Identifier: Fundación Canaria Instituto de Investigación Sanitaria de Canarias (FIISC))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No