RECOVER-NEURO: Platform Protocol to Measure the Effects of Cognitive Dysfunction Interventions on Long COVID Symptoms

Inclusion Criteria

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

• ≥ 18 years of age at the time of enrollment
• PROMIS-Cog T-score < 40
• Previous suspected, probable, or confirmed SARS-CoV-2 infection, as defined by the Pan American Health Organization

Suspected case of SARS-CoV-2 infection - three options, A through C:

A. Met clinical OR epidemiological criteria:

a. 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; b. Epidemiological criteria: Contact of a probable or confirmed case or linked to a COVID-19 cluster;

B. Presented 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; or

C. Presented 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 having met clinical criteria above AND was a contact of a probable or confirmed case or was linked to a COVID-19 cluster.

Confirmed case of SARS-CoV-2 infection - two options, A through B:

A. Presented with a positive nucleic acid amplification test, regardless of clinical criteria OR epidemiological criteria; or

B. Met clinical AND/OR epidemiological criteria (See suspected case A.a.), with a positive professional use or self-test SARS-CoV-2 Antigen-Rapid Diagnostic Test.

• Suspected and probable cases will only be allowed if they occurred before May 1, 2021, and will be limited to 10% of the study population. Otherwise, confirmed cases are required.
• Cognitive dysfunction symptoms following a SARS-CoV-2 infection that have persisted for at least 12 weeks and are still present at the time of consent
• Fluent in English or Spanish language
• Willing and able to provide informed consent, complete the intervention, complete the intervention assessments, and return for all of the necessary follow-up visits

Exclusion Criteria

An individual who meets any of the following criteria will be excluded from participation in this study:

• Prior or active unstable or progressive major psychiatric or neurologic condition that would not show improvement and could hide treatment effect and is not related to SARS-CoV-2 infection, at the investigator's discretion, including, but not limited to, the following examples:

a. Progressive neurodegenerative disease, such as Alzheimer's disease, Parkinson's disease, etc.

b. Past traumatic brain injury occurrence still associated with active post-concussive symptoms c. Uncontrolled seizure disorder, such as having at least one seizure in the last year that is adjudicated by clinical judgement d. Post-stroke deficits that may interfere with assessment, such as language or communication difficulties, aphasia, etc.

e. Formal thought disorders, such as schizophrenia, etc. f. Any neuropsychiatric or neurologic disorder uncontrolled for the previous six months or that may interfere with assessment, at discretion of the investigator

• Known prior diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome, not related to SARS-CoV-2 infection
• Known active acute SARS-CoV-2 infection ≤ 4 weeks from consent
• Current use of symptomatic therapies including prescribed or illicit stimulants, amantadine, N-methyl-D-aspartate receptor antagonists (e.g., memantine, dissociative drugs)
• Current use of a stimulant for treating any PASC-related symptom
• Current diagnosis of alcohol and substance use disorders

a. Prior use disorders acceptable if abstinence achieved and maintained for at least 12 months before study enrollment

• Insufficient visual, auditory, and motor function to participate in interventi