Multimodal Investigation of Post COVID-19 in Females

Study Overview
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Brief Summary
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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.

Detailed Description
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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).

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

Conditions
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Post COVID-19, Cognitive Dysfunction

Intervention / Treatment
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* Device: Parasym Device (of Parasym Ltd, UK) using Transcutaneous Vagus Nerve Stimulation (t-VNS)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transcutaneous Vagus Nerve Stimulation (t-VNS)<br>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)<br>* Electrode clip will be placed on the left ear.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRI, Long COVID, Post COVID-19 Syndrome, COVID long-haulers, Brain fog, Anosmia/Hyposmia, Neurological symptoms, Genetics, Inflammation, Transcutaneous vagus nerve stimulation, Fatigue, Anxiety, Depression, Cognitive impairment, EEG