Cognitive-Sensorimotor Function in Long-COVID

Enhancing Veterans Long-COVID Care: A Cognitive-Sensorimotor Framework to Understand Gait and Balance Dysfunction

Growing evidence indicates that many people who have chronic post-acute sequelae of SARS-CoV-2 infection (PASC) will experience ongoing neurological and musculoskeletal impairment that can affect gait and balance. Identifying the factors contributing to these impairments and how they influence functional mobility is the first step towards creating effective evaluation and treatment protocols. In this study the investigators will examine cognition, vision, proprioception, muscle strength, gait and balance in persons with and without PASC to understand how PASC may impact functional mobility through a cognitive-sensorimotor lens. Gait and balance will be studied in environments that stress cognitive and sensory abilities. Study outcomes will be critical for the development of evidence-based Veteran Health Administration diagnostic and standard-of-care protocols to address gait and balance dysfunction in Veterans with PASC for restoring their functional mobility and independence.

Study Overview

• Status: Recruiting
• Conditions: Post-acute Sequelae of SARS-CoV-2 Infection

Detailed Description

As many as one in seven COVID-19 survivors will experience symptoms that persist more than two months after their acute illness has resolved. Growing evidence estimates that up to 30% of people who experience this chronic post-COVID disorder (aka post-acute sequelae of SARS-CoV-2 infection (PASC)) will exhibit gait and balance dysfunction. The consequences of impaired mobility are of considerable concern for the Veterans Health Administration (VHA) given that mobility is closely related to quality of life for older adults and almost half of Veterans are 65 years or older. There currently is no established VHA standard-of-care for PASC. The critical first step towards development of comprehensive clinical protocols to identify and treat PASC-related gait and balance dysfunction is understanding the contributing factors. PASC is characterized by diverse multi-organ system effects that has made it difficult to identify the causes of dysfunction. However, new data suggests frequently reported neurologic issues related to cognitive and sensorimotor impairment may be potential contributors to gait and balance dysfunction. While cognition, sensation, and muscle function can be measured in isolation, the effects of cognitive and sensory impairment on gait and balance are best detected using dual task tests (e.g., count backward by 7's while walking) that pair cognitive and motor function or tasks performed in complex environments that limit sensory feedback and/or stress sensory-motor integration (e.g., maintaining standing balance with eyes closed). However, such assessments are not included in the current recommended PASC gait and balance screening guidelines, thereby leaving a clinical gap in knowledge when evaluating and treating Veterans and non-Veterans with PASC-related gait and balance dysfunction.

Therefore, the proposed project will evaluate the effect of PASC on isolated cognitive-sensorimotor function (Aim 1), and cognitive-sensorimotor contributions to gait (Aim 2) and balance (Aim 3) dysfunction in COVID-19 survivors through an observational cross-sectional study design. Aim 1 will assess cognition, vision, proprioception, and muscle strength independent of functional task in COVID-19 survivors with and without PASC using established methods. Aim 2 will perform an instrumented assessment of gait performance of participants under a dual task scenario to stress cognition. Aim 3 will perform an instrumented assessment of postural balance under different conditions that challenge sensorimotor integration by compromising certain sensory modalities (vision, vestibular, somatosensory). A non-instrumented clinical outcome measure will also be performed as a secondary measure to evaluate a potential clinical screening tool. Based on emerging evidence, the investigators hypothesize that COVID-19 survivors with PASC will exhibit worse cognitive-sensorimotor function, dual task gait performance, and sensory-interaction balance performance than those without PASC when accounting for age, sex, and time since acute infection. PASC-induced gait and balance dysfunction has significant clinical implications as it could compromise mobility, long-term health, and quality of life of Veterans if left unaddressed.

• Study Type: Observational
• Enrollment (Estimated): 136

Contacts and Locations

• Study Contact: Name: Keith E Gordon, PhD; Phone Number: 28387 (708) 202-8387; Email: Keith.Gordon2@va.gov
• Study Contact Backup: Name: Matthew J Major, PhD; Phone Number: (312) 569-6166; Email: Matthew.Major2@va.gov

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Recruiting
      • Jesse Brown VA Medical Center, Chicago, IL
      • Contact: Karen M Lenehan; Phone Number: (312) 569-6343; Email: Karen.Lenehan@va.gov
      • Contact: Matthew J Major, PhD; Phone Number: 312-569-6166; Email: Matthew.Major2@va.gov
      • Principal Investigator: Matthew J. Major, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Adults who previously contracted Covid-19 and do or do not have Long-COVID.

Description

Inclusion Criteria:

• Older than 18 years of age
• Positive PCR or Rapid COVID-19 test in the past
• Onset of COVID-19 illness greater than 3 months prior to their participation in the study
• Self-reported ability to walk 10 meters with or without external assistance prior to COVID-19 illness

Exclusion Criteria:

• Presence of severe cardiovascular and pulmonary disease and/or neurological and musculoskeletal disorders unrelated to COVID-19 (e.g., amputation, stroke, spinal cord injury)
• Cognitive impairments precluding ability to provide informed consent.
• Severe acute COVID-19 infection requiring hospitalization or diagnosed post-intensive care syndrome.
• Presence of musculoskeletal, inflammatory, or neurological conditions mimicking Long COVID-19 symptoms (e.g., concussion within last 5 years, Chronic fibromyalgia, Myofascial pain syndrome, etc.)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Control; Adults who previously contracted Covid-19 but do not have Long-COVID.
Experimental; Adults who previously contracted Covid-19 and have Long-COVID.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NIH Toolbox Cognition Battery	The NIH Toolbox Cognition Battery to assess working memory and attention cognitive function. Working memory and attention cognitive function are quantified through performance on the List Sorting Working Memory Test and Flanker Inhibitory Control and Attention Test, respectively, administered via tablet. Raw scores from these measures can be converted to normally distributed standard (scaled) scores adjusted for age, education, sex, and/or race/ethnicity (T-Scores), as appropriate. A higher score means better performance.	During single session of two hours
Joint position sense proprioception	Joint position sense is measured by participants' ability to accurately extend the knee joint to a target reference angle. Participants will be seated and perform nine trials where they have to replicate guided knee joint angle position of 30, 45, or 60°. The difference between guided and replicated position is recorded as the angle error, where greater error means worse proprioception.	During single session of two hours
King-Devick Test	The King-Devick Test assesses ocular-motor function. Participants are asked to accurately and rapidly read rows of single-digit numbers displayed on a tablet. The test score is calculated as the total time required to read three test cards (each test card is approximately a full page of numbers), where faster is better.	During single session of two hours
Maximum voluntary muscle strength	Participants will be seated and isokinetic maximum voluntary contraction is measured with a dynamometer, normalized by participant height and body mass (N-m/kg-m). Greater values mean better strength.	During single session of two hours
Dual task gait cost	Participants will walk at their self-selected speed for 10 laps back and forth along a 10-m straight walkway with wide turns, once without a cognitive task (single task) and once with a cognitive task that stresses working memory (dual task). Difference in gait speed (m/s) is the dual task gait cost, in which higher values mean worse performance.	During single session of two hours
Modified Clinical Test of Sensory Interaction on Balance	Participants stand on a force plate and perform four balance tasks for which participants are instructed to maintain quiet upright balance: 1) eyes open on a firm surface while focusing straight ahead (access to all three modalities), 2) eyes closed on a firm surface (compromised visual), 3) eyes open on a foam surface while focusing straight ahead (compromised somatosensory), and 4) eyes closed on a foam surface (compromised visual and somatosensory). Total CoP distance travelled (mm) of the four specific balance tasks is measured, with greater distance meaning worse performance.	During single session of two hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mini-Balance Evaluation Systems Test	The Mini-Balance Evaluation Systems Test is a performance-based clinical outcome measure to assess dynamic balance, including 14 items scored on a 3-level ordinal scale (total score of 28). The test assesses anticipatory postural adjustments, reactive postural control, sensory orientation, and dynamic gait. A higher summary score means better performance.	During single session of two hours

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: Edward Hines Jr. VA Hospital
• Investigators: Principal Investigator: Matthew J. Major, PhD, Jesse Brown VA Medical Center, Chicago, IL; Principal Investigator: Keith Edward Gordon, PhD, Edward Hines Jr. VA Hospital, Hines, IL

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2026
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: February 26, 2025
• First Submitted That Met QC Criteria: February 26, 2025
• First Posted (Actual): February 27, 2025

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Post-Infectious Disorders; COVID-19; Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Pathological Conditions, Signs and Symptoms; Post-Acute COVID-19 Syndrome
• Other Study ID Numbers: F5372-R; RX005372 (Other Grant/Funding Number: Dept Veterans Affairs)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No