Blood-Brain Barrier Integrity and Immune Dynamics in Neuropsychiatric Sequelae of Post-SARS-CoV-2 Onset ME/CFS Versus Pre-Pandemic ME/CFS Patients

Inclusion criteria

• Inclusion criteria for pre-pandemic onset ME/CFS cohort:
• 18-70 years of age
• At least 8th grade education
• Onset of the following symptoms prior to July 2019 (Pre-SARS-CoV-2 pandemic) and meeting 2015 IOM diagnostic criteria for MECFS:
• Substantial reduction in functioning and persistent and profound fatigue for at least 6 months. The person is unable to undertake the same level of activity before they became - . Their fatigue is not the result of significant exertion and is not substantially alleviated by rest.
• Post-exertional malaise.
• Unrefreshing sleep
• At least one of the following two symptoms:
• Cognitive impairment (difficulty with memory, finding words, understanding etc).
• Orthostatic intolerance (symptoms like palpitations, sweating, dizziness, nausea when standing that are reduced or eliminated when lying down).

Inclusion criteria

post SARS-CoV-2 onset ME/CFS:

• 18-70 years of age
• At least 8th grade education
• Previous suspected, probable, or confirmed SARS-CoV-2 infection, as defined by the World Health Organization:
• Suspected case of SARS-CoV-2 infection
• Three options, A through C:

Meets the clinical OR epidemiological criteria.

• Clinical criteria: Acute onset of fever AND cough (influenza-like illness) OR Acute onset of ANY THREE OR MORE of the following signs or symptoms: fever, cough, general, weakness/fatigue, headache, myalgia, sore throat, coryza, dyspnea, nausea, diarrhea, anorexia.
• Epidemiological criteria: Contact of a probable or confirmed case or linked to a COVID-19 cluster; or B. Presents with acute respiratory infection with history of fever or measured fever of ≥ 38°C; and cough; with onset within the last 10 days; and who requires hospitalization) C. Presents with no clinical signs or symptoms, NOR meeting epidemiologic criteria with a positive professional use or self-test SARS-CoV-2 antigen-Rapid Diagnostic Test.
• Probable case of SARS-CoV-2 infection, defined as meets clinical criteria above AND is a contact of a probable or confirmed case or is linked to a COVID-19 cluster.
• Confirmed case of SARS-CoV-2 infection - Two options, i. and ii.:
• A person with a positive nucleic acid amplification test, regardless of clinical criteria OR epidemiological criteria; or
• Meeting clinical criteria AND/OR epidemiological criteria (See suspect case A). With a positive professional use or self-test SARS-CoV-2 Antigen-Rapid Diagnostic Test.
• Post SARS CoV 2 onset of the following symptoms, meeting 2015 IOM diagnostic criteria for ME/CFS:
• Substantial reduction in functioning and persistent and profound fatigue for at least 6 months. The person is unable to undertake the same level of activity before they became - - Their fatigue is not the result of significant exertion and is not substantially alleviated by rest.
• Post-exertional malaise.
• Unrefreshing sleep.
• At least one of the following two symptoms:
• Cognitive impairment (difficulty with memory, finding words, understanding etc).
• Orthostatic intolerance (symptoms like palpitations, sweating, dizziness, nausea when standing that are reduced or eliminated when lying down).
• Given that our application focuses on MECFS patients with neuropsychiatric symptoms the investigators will require participants to report >1 symptom with at least one of the symptoms being neuropsychiatric in nature (e.g., brain fog, anxiety, depression, headaches).

Exclusion both groups (pre-pandemic onset ME/CFS and post SARS-CoV-2 onset ME/CFS):

• History of Axis I psychiatric disorders (including alcohol and drug dependence) except for mood disorders which developed after onset of ME/CFS symptoms.
• Severe or unstable medical condition that would interfere with physical participation.
• Neurological disorders, such as stroke, epilepsy, multiple sclerosis, Parkinson's disease, or dementia.
• History of severe head injury that resulted in persistent traumatic brain injury sequelae.
• Any condition that is contraindicated for the MRI environment (e.g., metal in the body, pacemaker, claustrophobia)
• Currently pregnant.
• Lack of English proficiency (to ensure validity in verbal outcome measures)
• Active or recent (within 3 months) substance misuse (which is known to affect BBB permeability) assessed by clinical interview and toxicology (nicotine/cannabis allowed)
• History of psychosis