Addressing Cognitive Fog in Long-COVID-19 Patients

This study will assess two options to help patients better manage the cognitive fog and emotional distress that may be associated with having Long-COVID. Long-COVID is post-COVID conditions or symptoms lasting more than four weeks after infection. Clinicians from the UPMC Long-COVID Clinic leading this study are evaluating the utility of computer-based evaluation of COVID-related cognitive fog and the helpfulness of two intervention strategies to treat moderate cognitive impairment using a randomized trial. The two intervention strategies include 1) a standardized dosing of amphetamine/dextroamphetamine medication that has been used to improve cognitive fog; and 2) a digital behavioral tool with an embedded health coach that is used on a mobile phone.

Eligible participants will be randomized to one of two arms. One intervention targets cognitive fog associated with depression (RxWell mobile app), the other the cognitive fog directly (Amphetamine-dextroamphetamine medication). Two weeks after randomization, participants are contacted by study staff to complete the GAD7. Participants who are randomized to RxWell will be offered assistance if they were not able to download the app on their own. Participants who are randomized to receive the stimulant will also complete a stimulant drug side effect rating scale to determine if the participant has any effects from the medication.

All participants will complete computerized neurocognitive assessments (ImPACT, and BrainCheck) and other study measures (MOCA (Screen, 1.5 and 3 months), Patient Health Questionnaire, Generalized Anxiety Disorder Measure, Satisfaction with Life Scale, PCL-5 Post Traumatic Stress Disorder checklist, ADHD Symptom Screener, and Sheehan Disability Scale) at baseline, 1.5 (interim) and 3 months after randomization. The study measures, other than the neuro-cognitive assessments, will be completed via REDCap.

Eligibility Criteria:
Inclusion Criteria:

* History of SARS-CoV-2 infection as defined as a positive PCR or home antigen test
* Patients with Long-COVID as defined as COVID symptoms that persist for three months or longer.
* Between the ages of 21 and 65
* Moderate cognitive impairment (MOCA score to meet criteria is \< or =18) present for at least 3 months
* Response of "No" to the screening question, "Are you pregnant or do you plan to become pregnant in the next 3 months?"
* Access to a smartphone

Exclusion Criteria:

* History of dementia, psychosis, mania, addiction or current conditions requiring immediate hospitalization
* Previous adverse or allergic reaction to Adderall or other amphetamines
* Pre-existing cardiac or kidney condition, severe hypertension, glaucoma, advanced arteriosclerosis, hyperthyroidism, and taking an MAOI within the past 14 days
* Current or past substance misuse
* Previous use of RxWell (completed 3 or more techniques)
* Current use of amphetamine-dextroamphetamine
* History of uncontrolled blood pressure
* Subjects taking Methylphenidate; Lisdexamfetamine; non-Adderall amphetamine products; Atomoxetine; Viloxazine; Modafinil; Armodafinil; Nortriptyline and other tricyclic drugs; Bupropion; Tramadol; and Monoamine Oxidase Inhibitor (MAOI) drugs (including Linezolid).
* Inability to pay for study medication.