Neural and Cognitive Consequences of COVID-19 Survival

The novel coronavirus SARS-CoV-2 infection, COVID, continues to rage throughout the world with 115,000,000 confirmed cases and over 2,500,000 deaths (as of Mar 3, 2021). This translates to millions of people surviving COVID19 infection. While the lungs are ground zero, COVID tears through organ systems from brain to blood vessels. We are now beginning to see people recover but complain of ongoing problems, including lingering cognitive problems, depression, and anxiety. We have brought together 2 laboratories with complementary techniques including psychological testing and neuroimaging methods togethers with markers in the blood that may signal damage in the brain. A close look at these problems is timely and imperative if we are to understand the pathophysiology of 'COVID brain' and prepare for downstream problems.

Study Overview

• Status: Recruiting
• Conditions: COVID-19; Fatigue; COVID-19 Pandemic; Concentration Ability Impaired; Memory Deficits; Brain Fog; COVID Long-Haul
• Intervention / Treatment: Other: cross-sectional MRI and EEG assessments (NO INTERVENTION)

Detailed Description

The SARS-CoV-2 pandemic has been going on for over a year worldwide, with 115,000,000 confirmed cases and over 2,500,000 deaths (as of Mar 3, 2021). We are seeing people recover from the initial COVID infection with complaints of ongoing problems. An increasing number of people are complaining of cognitive deficits and depression/anxiety.

Methodologically, we have brought together two laboratories studying neurocognitive impairment using an EEG, MRI, and behavioral approach as well as laboratory-based data. This study queries neuropsychological functions in individuals using a neuropsychological battery, EEG-based measures, functional MRI (connectivity) and structural MRI (gray and white matter volumes, myelin, micro-bleeds). In addition, we have preliminary data to show a continued increase in plasma cytokines in COVID survivors. Plasma isolated neuronal enriched extracellular vesicles (nEVs) showed an increase in amyloid beta, neurofilament light and pT181-Tau, all proteins associated with neurodegeneration.

The overall aim is to determine the extent of cognitive, clinical, and neurological damage in people recovered from COVID.

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Kaitlyn L Dal Bon, BA; Phone Number: (415) 629-9514; Email: kaitlyn.dalbon@ucsf.edu
• Study Contact Backup: Name: Ken Lau, BS; Phone Number: (415) 562-4334; Email: ken.lau@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94121
      • Recruiting
      • San Francisco Heathcare System
      • Principal Investigator: Judith M Ford, PhD
      • Contact: Kaitlyn L Dal Bon, BA; Phone Number: 415-629-9514; Email: kaitlyn.dalbon@ucsf.edu

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Individuals 18-70 years old who were diagnosed with COVID-19 at least 3 months ago.

Description

Inclusion Criteria:

• Our studies require some in-person visits to our research lab, located at 42nd Ave and Clement St in San Francisco.
• Because this study includes an MRI, part of the screening process will be to ensure you don't have any metal in your body, you do not have head or neck tattoos, and you are comfortable inside the MRI scanner.
• 18-70 years with a confirmed COVID infection at least 3 months ago.
• Negative metal screen for MRI safety
• Normal (or corrected to normal) vision

Exclusion Criteria:

• Past or present neurological problems (including seizures and head trauma resulting in neurological or cognitive symptoms)
• Loss of consciousness (LOC) greater than 30 minutes or any LOC with neurologic symptoms
• Major medical conditions (e.g., seizures disorders, treatment with anticonvulsant medication, endocrine disorders, significant cardiac pathology)
• Substance dependence, within the past year, or failed urine toxicology on the day of neuroimaging sessions
• Known claustrophobia
• Current pregnancy
• IQ estimate < 70

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
NeuroCOVID Group; Individuals (ages 18-70 years) who endorse a reported change in concentration, memory, feelings anxiety or depression since initial COVID infection.	Other: cross-sectional MRI and EEG assessments (NO INTERVENTION); n/a there is no intervention in this observational study; Other Names: cross-sectional MRI and EEG assessments
COVID Control Group; Individuals (ages 18-70 years) who do not feel any different since recovering from initial COVID infection.	Other: cross-sectional MRI and EEG assessments (NO INTERVENTION); n/a there is no intervention in this observational study; Other Names: cross-sectional MRI and EEG assessments

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of Neuropsychological Test Performance	We will compare NP test performance in people with Covid-related worsening of attention, memory, anxiety, and/or depression to people who do not endorse worsening in those domains.	1 month
Number of Participants with EEG Latency & Amplitude	We will compare EEG-derived event related potential measures of neural speed in people with Covid-related worsening of attention, memory, anxiety, and/or depression to people who do not endorse worsening in those domains.	1 month
Number of Participants with MRI Functional Disconnectivity	We will compare thalamo-cortical connectivity in people with Covid-related worsening of attention, memory, anxiety, and/or depression to people who do not endorse worsening in those domains.	1 month
Number of Participants with Blood Biomarkers	We will correlate blood biomarkers of inflammation and NP test performance, thalamo-cortical connectivity, and measures of neural speed.	1 month

Collaborators and Investigators

• Sponsor: San Francisco Veterans Affairs Medical Center
• Investigators: Principal Investigator: Judith M Ford, PhD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2021
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): September 30, 2025

Study Registration Dates

• First Submitted: January 11, 2024
• First Submitted That Met QC Criteria: January 11, 2024
• First Posted (Actual): January 17, 2024

Study Record Updates

• Last Update Posted (Actual): April 12, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: MRI; fatigue; functional MRI; fMRI; EEG; long COVID; brain fog; difficulty concentrating; memory difficulty
• Additional Relevant MeSH Terms: Behavioral Symptoms; Nervous System Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; COVID-19; Fatigue; Memory Disorders; Mental Fatigue
• Other Study ID Numbers: CX002322

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Not part of currently approved protocol or original agreement with sponsor.

Drug and device information, study documents

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