Inclusion Criteria:

• - Adults ≥ 18 years of age.

• - Approval from the patient's primary inpatient service.

• - Hospitalized.

• - Diagnosed with COVID-19 pneumonia.

• - Positive test for active SARS-CoV-2 infection.

• - Requiring supplemental oxygen ≥ 5LNC or ≥ 40% FiO2.

• - Chest computed tomography (CT) at admission with < 10% pulmonary fibrosis.

• - Ability to provide written informed consent on the part of the subject or, in the absence of decisional capacity of the subject, an appropriate surrogate (e.g. a legally authorized representative).

Exclusion Criteria:

• - Known diagnosis of previous pulmonary fibrosis or an interstitial lung disease.

• - Clinical features or known diagnosis of malignancy or active non-COVID-19 infection, including untreated latent tuberculosis.

• - History of unstable or deteriorating cardiac disease (including myocardial infarction, coronary artery bypass surgery or angioplasty within the past 6 months, congestive heart failure requiring hospitalization within the past 6 months, or uncontrolled arrhythmia.

• - Known history of hypersensitivity to sirolimus.

• - History of unstable or deteriorating neurologic disease (including TIAs or stroke).

• - Pregnant or lactating females.

Females of child bearing potential are required to have a negative pregnancy test prior to treatment and practice abstinence or prevent pregnancy by at least a barrier method of birth control.

• - Investigational therapy for any indication within 28 days prior to treatment.

• - Current treatment with any drugs that are strong inhibitors of CYP3A4.

• - Tofacitinib.

• - Clarithromycin.

• - Telithromycin.

• - Nefazodone.

• - Itraconazole.

• - Ketoconazole.

• - Atazanavir.

• - Darunavir.

• - Indinavir.

• - Lopinavir.

• - Nelfinavir.

• - Ritonavir.

• - Saquinavir.

• - Tipranavir.

• - Inability or unwillingness to comply with the requirements for the trial.

Hospitalized patients with a diagnosis of COVID-19 pneumonia will be referred to the study team for potential recruitment. Initial screening will take place using the existing medical record and in collaboration with the treating team. The study consists of 3 randomly assigned arms of varying dosages of the study drug. All procedures, with the exception of drug dosing and option sample analysis, align with the subject's standard of care. Prior to initiating study drug, the subject's standard of care labs, imaging and oxygen requirements will be reviewed. Sirolimus will be administered as an oral medication. Subjects who are discharged prior to receiving 14 days of study drug will be provided with enough study drug to finish at home. On-study evaluation includes measurement of vital signs and laboratory studies before and after a patient has received sirolimus while inpatient. As part of routine care, subjects will be seen daily while in the hospital and will be monitored through blood tests for general health as well as renal function. Vital signs will be monitored daily while in the hospital, physical exams, assessment of COVID-19, and CT scans or chest x-rays as necessary for routine care. Subjects will return to clinic at 12 weeks for routine lab work and imaging as a part of study follow-up and will be assessed for pulmonary fibrosis at this time. Additionally, University of Chicago Medicine patients will have the option to allow investigators to use leftovers from tubes of blood drawn for clinical tests that would otherwise be discarded. This will apply to any blood collected during that respective hospital stay as well as up to 1 year after study enrollment.

Arms

Active Comparator: Sirolimus 0.5mg

Subject will take Sirolimus 0.5mg orally daily for 14 days.

Active Comparator: Sirolimus 1mg

Subject will take Sirolimus 1mg orally daily for 14 days.

Active Comparator: Sirolimus 2mg

Subject will take Sirolimus 2mg orally daily for 14 days.

Interventions

Drug: - Sirolimus

Triangular-shaped tablet