The goal of this study is to determine whether a medicine called tirzepatide, also called Zepbound, can reduce symptoms of Long COVID. A randomized control trial will allow us to measure the effect of the treatment by having half of the participants take the medication and half take a placebo that has no medication. Participants will take the medication (or placebo) they are given and complete study surveys for 12 months. All of the study tasks are done remotely from the comfort of a participants home.

Inclusion Criteria:

• 18 years of age or older Living in the United States Able to read and understand English or Spanish Willing and able to participate in study interventions and activities, including;
• Access to an internet connected device
• Informed Consent
• Surveys
• Medication schedule
• Adverse Event reporting
• Weight reporting
• Use of wearable activity tracker
• Completing at home blood collections, if selected Meets the NASEM definition of Long COVID: an infection-associated chronic condition that occurs after SARS-CoV-2 infection and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems 16.

Ability to verify identity Ability to verify diagnosis Agree to notify the study team if you start any other Long COVID treatments while enrolled in the study.

Complete the Fatigue Severity Scale with a minimum score of 36

Exclusion Criteria:

• Certain vulnerable populations (prisoners, children, fetuses, and institutionalized individuals)
• Women who are pregnant, excluded due to unknown risks to a fetus
• Personal or family history of medullary thyroid carcinoma
• History of severe gastrointestinal disease
• Diagnosis of gastroparesis
• Worsening or chronic renal failure
• History of pancreatitis
• Multiple Endocrine Neoplasia syndrome type 2
• Known serious hypersensitivity to tirzepatide
• Already taking tirzepatide or another GLP-1 agonist
• Medication contraindications to tirzepatide
• History of suicidal attempts and/or active suicidal ideation
• Underweight (BMI under 18.5)
• Planning to undergo elective surgery or procedures requiring general anesthesia or deep sedation in the next 12 months
• Symptoms of fatigue and/or brain fog that predated infection with COVID-19

The investigators may share the coded study data with researchers outside of Scripps Research. Before doing so, they will ensure that nothing in the data can identify the participant directly.