Multimodal Investigation of Post COVID-19 in Females

Multimodal Investigation of Post COVID-19 in Females: A Pilot Study

The purpose of this study is to investigate the effects of transcutaneous vagus nerve stimulation (t-VNS) on Long Covid symptoms in females and to identify factors influencing susceptibility and recovery-particularly in the cognitive domain, as over 80% of long-haulers experience "brain fog".

Study Overview

• Status: Completed
• Conditions: Cognitive Dysfunction; Post COVID-19
• Intervention / Treatment: Device: Parasym Device (of Parasym Ltd, UK) using Transcutaneous Vagus Nerve Stimulation (t-VNS)

Detailed Description

Long COVID is a post-viral illness estimated to affect 10-30% of COVID-19 patients. Post-COVID symptoms can last for months and affect multiple organs. Major risk factors of long COVID include the female sex and pre-existing anxiety/depression. Because women already have higher rates of anxiety/depression, the combined risks could exacerbate their susceptibility.

Based on the rationale that long COVID symptoms significantly overlap with functions of the vagus nerve, which serves as a conduit between the brain and body, the investigators propose to use non-invasive transcutaneous vagus nerve stimulation (t-VNS) as a novel treatment for long COVID in 20 female participants.

This pilot study will utilize a holistic approach by integrating neuromodulation, neuroimaging, genetics, blood biomarkers, behavioral assessments, and wearable technology to examine the effects of VNS therapy on post COVID-19 symptoms and to identify factors that influence susceptibility and recovery, particularly in the cognitive domain, as over 80% of long-haulers report experiencing "brain fog" (i.e., cognitive disruptions).

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Pomona, California, United States, 91769
      • Casa Colina Hospital and Centers for Healthcare

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Biologically female at birth and at time of enrollment
• At least 18 years of age or older
• Experiencing persistent symptoms of brain fog/cognitive impairment beyond 3 months of COVID-19 infection that are not explained by an alternative diagnosis

Exclusion Criteria:

• Not t-VNS compatible (e.g. pacemaker implants)
• Not MRI compatible (e.g. metal implants, claustrophobia)
• Currently pregnant
• Long COVID without cognitive impairment
• History of neurological conditions prior to COVID-19 infection

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: Transcutaneous Vagus Nerve Stimulation (t-VNS); Participants will receive 60 minutes of t-VNS stimulation every day for 10 consecutive days while wearing a fitness tracker.	Device: Parasym Device (of Parasym Ltd, UK) using Transcutaneous Vagus Nerve Stimulation (t-VNS); Electrode clip will be placed on the left ear.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Flanker Inhibitory Control and Attention Test (Flanker) scores	Flanker is a non-verbal NIH Toolbox Cognition Battery assessment that measures both a participant's attention and inhibitory control.	At baseline, at week 3, and at week 7
Change in Picture Sequence Memory Test (PSMT) scores	PSMT is a non-verbal NIH Toolbox Cognition Battery assessment that measures a participant's episodic memory.	At baseline, at week 3, and at week 7
Change in Dimensional Change Card Sort Test (DCCS) scores	DCCS is a non-verbal NIH Toolbox Cognition Battery assessment that measures a participant's executive functioning.	At baseline, at week 3, and at week 7
Change in Pattern Comparison Processing Speed scores	Pattern Comparison Processing Speed is a non-verbal NIH Toolbox Cognition Battery assessment that measures a participant's processing speed.	At baseline, at week 3, and at week 7
Change in List Sorting Working Memory scores	List Sorting Working Memory is an oral NIH Toolbox Cognition Battery assessment that measures a participant's working memory.	At baseline, at week 3, and at week 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Magnetic Resonance Imaging (MRI)	MRI scans will be acquired on a Siemens Magnetom Verio 3T Scanner at Casa Colina Imaging Center to assess structural changes.	At baseline and at week 3
Change in resting state Electroencephalograph (EEG) signals	Using a 64-channel EEG system, we will perform resting-state EEG recordings to assess power spectral density changes.	At baseline and at week 3
Change in blood marker levels	Blood markers related to COVID-19, inflammation, brain injury, and neuroplasticity will be analyzed using the Ella automated immunoassay system.	At baseline and at week 3
Change in BURNS Anxiety Inventory scores	The BURNS Anxiety Inventory is a self-reported rating scale that measures anxiety symptoms.	At baseline, at week 3, and at week 7
Change in Becks Depression Inventory (BDI) scores	The BDI is a self-reported rating inventory that measures characteristic attitudes and symptoms of depression.	At baseline, at week 3, and at week 7
Change in PROMIS Sleep Disturbance scores	The PROMIS Sleep Disturbance (8b) is a self-reported measure for perception of sleep quality, depth of sleep, satisfaction with sleep, and perception of difficulty getting and staying asleep.	At baseline, at week 3, and at week 7
Change in Fatigue Severity Scale scores	The Fatigue Severity Scale is a self-reported 9-item scale which measures the severity of fatigue and its effect on a person's activities and lifestyle in patients with a variety of disorders.	At baseline, at week 3, and at week 7
Change in Sniffin' Sticks olfactory performance	The Sniffin' Sticks test (Burghardt®, Wedel, Germany) assesses odor threshold, odor discrimination, and odor identification.	At baseline, at week 3, and at week 7

Collaborators and Investigators

• Sponsor: Casa Colina Hospital and Centers for Healthcare
• Investigators: Principal Investigator: Amy Zheng, PhD, Casa Colina Hospital and Centers for Healthcare

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2022
• Primary Completion (Actual): January 6, 2023
• Study Completion (Actual): January 6, 2023

Study Registration Dates

• First Submitted: February 2, 2022
• First Submitted That Met QC Criteria: February 2, 2022
• First Posted (Actual): February 4, 2022

Study Record Updates

• Last Update Posted (Actual): July 7, 2023
• Last Update Submitted That Met QC Criteria: July 5, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: MRI; Genetics; Depression; Inflammation; Anxiety; Fatigue; Cognitive impairment; EEG; Long COVID; Transcutaneous vagus nerve stimulation; Post COVID-19 Syndrome; COVID long-haulers; Brain fog; Anosmia/Hyposmia; Neurological symptoms
• Additional Relevant MeSH Terms: Mental Disorders; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Neurocognitive Disorders; Cognition Disorders; COVID-19; Cognitive Dysfunction
• Other Study ID Numbers: IRB#00002372

Drug and device information, study documents

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