Neural Mechanisms of Fatigue in Post-Acute Sequela of SARS-CoV-2

NCT07278388 | Recruiting

• 2 other identifiers: IRB00283000_1R01NS140610
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

This proposal aims to understand the neurobiological mechanisms of fatigue in individuals with Post-Acute Sequelae of SARS-CoV-2 Infection (PASC). This knowledge will eventually provide candidate mechanisms to target with pharmacological intervention and inform rehabilitative care for those individuals suffering from symptoms of fatigue in PASC.

Conditions

PASC Post Acute Sequelae of COVID 19; Fatigue

Outcome Measures

Primary Outcomes (12)

• Comparison between PASC and HC - difference in mean Assessment Error

  The difference between the level of effort rated by participants, and their average grip force exerted on a grip force dynamometer. Compared between PASC and HC.

  Baseline, during experimental protocol.

• Comparing between PASC and HC - difference in BBB permeability

  Collected from and MRI sequence designed to measure BBB permeability.

  Baseline, during MRI acquisition.

• Comparing between PASC and HC - Regions of the brain that are sensitive to Assessment error as a function of disease state

  We will examine an fMRI contrast, at the time of effort assessment, between HC and PASC groups. This contrast will examine percent signal change in brain activity.

  Baseline, during experimental protocol.

• The modulatory effect of BBB permeability on the relationship between Neural Activity and Effort Assessment

  We will create a structural equation model that includes BBB permeability, fMRI activity, effort assessment behavior, and disease state (PASC/HC).

  Baseline, during experimental protocol and MRI aquisition.

• Comparing between PASC and HC - Difference in momentary subjective fatigue ratings

  Measures of subjective fatigue will be collected on self report scale that ranges from 'not fatigued at all' to 'very fatigued'.

  Baseline and during fatiguing exertions in the experimental protocol.

• Comparing between PASC and HC - Difference in Mean Acceptance Rate of Risky Effort Options between rested/baseline and fatigue choices

  Proportion of decisions in which inviduals choice to accept a risky effort opitions over a sure effort option.

  Baseline and during fatiguing exertions in the experimental protocol.

• Comparing between PASC and HC - Regions of the brain encoding a difference in effort cost between rested/baseline and fatigue choices

  We will examine a contrast between chosen effort value pre versus post fatigue, between the HC and PASC groups. This contrast will examine percent signal change in brain activity.

  Baseline and during fatiguing exertions in the experimental protocol.

• The modulatory effect of BBB permeability on the relationship between Neural Activity and change effort-based decision-making

  We will create a structural equation model that includes BBB permeability, fMRI activity, change in effort-based decision-making, and disease state (PASC/HC).

  Baseline, fatigueing exertion, and during experimental protocol and MRI aquisition

• Comparing between PASC and HC - Difference in mean assessment error as a function of time

  The difference between the level of effort rated by participants, and their average grip force exerted on a grip force dynamometer. Compared between PASC and HC.

  Data collections at months 0, 3, 6, 12

• Comparing between PASC and HC - Difference in momentary subjective fatigue ratings as a function of time

  Measures of subjective fatigue will be collected on self report scale that ranges from 'not fatigued at all' to 'very fatigued'.

  Data collections at months 0, 3, 6, 12

• Comparing between PASC and HC - difference in BBB permeability as a function of time

  Collected from and MRI sequence designed to measure BBB permeability.

  Data collections at months 0, 3, 6, 12

• Comparing between PASC and HC - Regions of the brain that are sensitive to Assessment error as a function of disease state and time

  We will examine a contrast, at the time of effort assessment, between HC and PASC groups, and use time as a covariate. This contrast will examine percent signal change in brain activity.

  Data collections at months 0, 3, 6, 12

Study Arms (2)

PASC Participants - Physical Fatigue Task

EXPERIMENTAL

Participants will perform a physically demanding task (grip force exertion task) repeatedly to induce physical fatigue.

Behavioral: Physical Fatigue

Control Participants - Physical Fatigue Task

EXPERIMENTAL

Participants will perform a physically demanding task (grip force exertion task) repeatedly to induce physical fatigue.

Behavioral: Physical Fatigue

Interventions

Physical Fatigue BEHAVIORAL

Participants will perform a physically demanding task (grip force exertion task) repeatedly to induce physical fatigue.

Control Participants - Physical Fatigue Task; PASC Participants - Physical Fatigue Task

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18 to 75 years old.
• Have received a clinical diagnosis of post-acute sequelae of SARS-CoV-2 (PASC)/long COVID syndrome using the criteria specified by Thaweethai, et al., 2023 (JAMA). This symptom checklist provides a score based on the number and severity of symptoms. An individual with a score \>12 is classified as having PASC.
• Currently experiencing Fatigue/Brain Fog as assessed with the Post-COVID symptom checklist and the PedsQL questionnaire.

You may not qualify if:

• Neurological disorders including, but not limited to, stroke, head injury, epilepsy, seizures, brain tumors, brain surgery, Parkinson's Disease, or any other neuromuscular disease (self-report).
• Diagnosed history of severe psychiatric diseases such as depression and schizophrenia (self-report).
• Congestive heart failure.
• Peripheral artery disease with claudication.
• Cancer.
• Pulmonary or renal failure.
• Unstable angina.
• Uncontrolled hypertension (more than 190/110 mmHg).
• Severe aphasia.
• Orthopedic or pain conditions.
• Have had exposure to metal or metal implants, due to the hazardous effects of the magnetic field.
• If on immunomodulatory therapy, they must have been on that therapy for at least 6 months before the start of the study.
• Hospitalization due to SARS-CoV-2 infection.
• Neurological disorders including, but not limited to, stroke, head injury, epilepsy, seizures, brain tumors, brain surgery, Parkinson's Disease, or any other neuromuscular disease (self-report).
• Diagnosed history of severe psychiatric diseases such as depression and schizophrenia (self-report).

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• Hugo W. Moser Research Institute at Kennedy Krieger, Inc.: lead

Study Sites (1)

Kennedy Krieger Institute

Baltimore, Maryland, 21201, United States

RECRUITING

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome; Fatigue

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms

Study Officials

• Vikram Chib, PhD

  Johns Hopkins University; Kennedy Krieger Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anthony Gonzalez

CONTACT

443-923-2716; gonzalezan@kennedykrieger.org

Vikram Chib, PhD

CONTACT

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2025
• First Posted: December 12, 2025
• Study Start: July 16, 2025
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: December 12, 2025

Record last verified: 2025-12

Locations

US (1)