Magnetic Resonance Analysis of Neural Inflammatory Factors and External Stimulation

Chronic neuropsychiatric symptoms of post-acute sequelae of COVID-19 (neuro-PASC) can lead to disability, loss of function, and reduced quality of life, but there are currently no validated effective treatments. We propose a randomized sham-controlled trial of "Magnetic Resonance Analysis of Neural Inflammatory Factors and External Stimulation (MANIFEST)." We will deliver active or sham accelerated iTBS (5x/day, 10 days, 25 blinded sessions followed by 25 open-label sessions) to each participant's brain target. We will assess neuro-PASC symptoms, mood, anxiety, cognition, and quality of life from baseline to end-of-treatment. We will correlate symptom improvement with clinical and imaging variables.

Inclusion criteria

• aged 18-80
• a documented diagnosis of PASC with evidence of ongoing symptoms as demonstrated by score of 12 on the NIH RECOVER Symptom List
• have "brain fog" or cognitive difficulties as one of the ongoing symptoms
• are fluent in English
• if taking psychotropic medications, have been on stable doses for the past month.

Exclusion criteria

• a prior history of other neurological disease, or any history of seizures, so as to reduce risk of exacerbation of epilepsy or other neurological symptoms;
• history of a psychotic disorder, such as schizophrenia or bipolar disorder, so as to reduce risk of psychiatric decompensation
• history of ongoing substance/alcohol dependence, to reduce confounding effects on diagnosis and brain imaging
• presence of any implanted electrical device (e.g., pacemaker), to reduce risk of device malfunction from rTMS
• recent medical hospitalization (within four weeks), to reduce risk of medical decompensation during the study
• any condition that would prevent the subject from completing the protocol
• appointment of a legal representative, to avoid coercion of a vulnerable population
• any ongoing litigation related to medical diagnosis, or disability, to prevent interference with legal proceedings
• any contraindication to MRI
• membership in an identified vulnerable population, including minors, pregnant women, and prisoners, so as to prevent coercion.