The primary purpose of this phase 2a study is to compare the efficacy of abrocitinib to placebo in improving severe fatigue in non-hospitalized adults with symptomatic Post-COVID Condition (PCC) (also called Long COVID). We are also interested in learning if abrocitinib is effective in improving overall health status in people suffering from severe fatigue from PCC. Eligible participants with a confirmed history of COVID19 infection who also have PCC according to the World Health Organization definition, will be randomized to receive abrocitinib at a dose of 50 mg, 100 mg, or placebo by mouth daily for 12 weeks (84 days).

Eligible volunteers will participate in six in-person visits at Beth Israel Deaconess Medical Center over 5 months. These visits include review of medical and medication history, answering questionnaires, blood, urine, and nasal swab specimen collection, physical exams, and contraceptive and medication counseling.

Inclusion Criteria:

• History of confirmed COVID-19 infection
• PCC diagnosis according to the WHO definition as occurring in individuals with a history of probable or confirmed SARS CoV-2 infection, usually 3 months from the onset of COVID-19 that lasts for at least 2 months and cannot be explained by an alternative diagnosis
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures
• Capable of giving signed informed consent

Exclusion Criteria:

• Participants with acute and chronic infections, history of specific recurrent infections
• Suspected or confirmed active SARS-CoV-2 infection within past 30 days
• Some cardiac conditions
• Any current tobacco smoker or person who has smoked tobacco products within 12 months of screening, or former tobacco smoker ≥ 50 years old
• Known to be infected with Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C, Herpes Virus, or Tuberculosis
• History of immunodeficiency
• Blood clotting conditions
• Must meet general screening laboratory criteria
• Allergy or other contraindication to any of the components of the study intervention
• Known prior participation in this trial or other trial involving abrocitinib
• Concurrent therapy with a JAK or TYK2 inhibitor
• Other protocol criteria apply