Multimodal Investigation of Post COVID-19 in Females

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".

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).

Long COVID, Post COVID-19 Syndrome, COVID long-haulers, Brain fog, Anosmia/Hyposmia, Neurological symptoms, EEG, MRI, Genetics, Inflammation, Transcutaneous vagus nerve stimulation, Fatigue, Anxiety, Depression, Cognitive impairment

Participants will receive 60 minutes of t-VNS stimulation every day for 10 consecutive days while wearing a fitness tracker.

Flanker is a non-verbal NIH Toolbox Cognition Battery assessment that measures both a participant's attention and inhibitory control.

PSMT is a non-verbal NIH Toolbox Cognition Battery assessment that measures a participant's episodic memory.

DCCS is a non-verbal NIH Toolbox Cognition Battery assessment that measures a participant's executive functioning.

Pattern Comparison Processing Speed is a non-verbal NIH Toolbox Cognition Battery assessment that measures a participant's processing speed.

List Sorting Working Memory is an oral NIH Toolbox Cognition Battery assessment that measures a participant's working memory.

MRI scans will be acquired on a Siemens Magnetom Verio 3T Scanner at Casa Colina Imaging Center to assess structural changes.

Using a 64-channel EEG system, we will perform resting-state EEG recordings to assess power spectral density changes.

Blood markers related to COVID-19, inflammation, brain injury, and neuroplasticity will be analyzed using the Ella automated immunoassay system.

The BDI is a self-reported rating inventory that measures characteristic attitudes and symptoms of depression.

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.

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.

The Sniffin' Sticks test (Burghardt®, Wedel, Germany) assesses odor threshold, odor discrimination, and odor identification.

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