This clinical trial will study the safety and efficacy of COVID-19-specific T cells when given as treatment to adult patients (age ≥ 18 years) with a COVID-19 infection. This immunologic treatment is aimed at patients, who are at high risk of progression due to their advanced age, or other underlying health conditions. The outcomes of patients receiving the T cells (Arm A) will be compared to patients treated with standard of care (Arm B).

T cells that recognize COVID-19 peptides will be manufactured at Thomas Jefferson University and are frozen and ready for use. The T cells have to have an immune protein called HLA in common with a patient to work. If a patient enrolled on the COVID-19 study has this HLA, they will receive a dose of the COVID-19 T cells. Groups of 3-6 patients will be treated at each testing dose level. There are four dose levels of T cells: 1 x 105/kg, 3 x 105/kg, 1 x 106/kg, and 3 x 106/kg. Patients will receive the T cells intravenously in the hospital and be monitored there for 4 days before being discharged. Before discharge, patients will be taught to take and record their temperature, blood pressure, and oxygen levels (using a finger monitor) at home. After discharge, study staff will continue to monitor patient symptoms and recordings with video visits or phone calls daily until the monitoring period of 14 days is over. Patients will also be asked to give blood samples 7, 14, 28, days and 2, 3, and 6 months after the T cells are given. Patients who meet study criteria and wish to participate but do not have the HLA protein in common with the T cells, will be monitored by study personnel in their own homes for the full 14 day period. These patients will also be taught to take and record their temperature, blood pressure, and oxygen level. Study personnel will contact them daily by video or voice calls and check on the results of their readings and their symptoms. These patients may be treated with any standard or experimental COVID-19 therapy. How patients handle their COVID-19 infection will be compared between the group of people receiving the T cells and the group of people who do not receive the T cells.

Inclusion Criteria:

Have a documented active COVID-19 infection and one of the following high-risk criteria:

• Malignancy receiving radiation or chemotherapy in the prior 24 months.
• Chronic lung disease such as asthma, COPD, interstitial lung disease, pulmonary hypertension or cystic fibrosis, requiring treatment beyond inhaled medications
• Hypertension either treated or with evidence of need for treatment
• Cardiovascular disease requiring active medical monitoring and care including heart failure, heart dysrhythmias, coronary artery disease, congenital heart disease, cardiomyopathy, or pulmonary hypertension
• History of ischemic stroke
• Diabetes (type 1, type 2, or gestational) requiring treatment with insulin or oral hypoglycemics
• Chronic Kidney Disease (Hx of stage 3b or greater as defined by the National Kidney Foundation)
• Chronic Liver Disease (Previously diagnosed with cirrhosis or previously classified as having Pugh-Child class A-C liver disease) oObesity (BMI >= 35) oSickle Cell Disease or Thalassemia
• Patients requiring nursing home support or who have a Karnofsky Performance Status of 70% or less antedating their COVID-19 illness.
• Age >= 65 (with or without previously identified comorbid conditions)

Exclusion Criteria:

• Matching their intended CTL product donor at 5 or 6 of 6 HLA-class I (HLA-A, B, and C) alleles.

• Requiring supplemental oxygen

• Evidence of active COVID-19-related CRS as evidenced by 2 or more of the following characteristics of cytokine storm:

  o> grade 1 CRS on ASTCT criteria. ASTCT criteria do not provide quantitative guidelines regarding the definition of hypotension. For this trial, hypotension will be defined as:

  1. requiring vasopressors

  2. Systolic blood pressure <90 mm Hg

  3. Diastolic B/P < 60 mm Hg NB Lower systolic and diastolic blood pressures will be acceptable if patient's blood pressure is at his/her known baseline.

     • Uncontrolled hypertension as defined by a systolic pressure of > 180 mm Hg or diastolic pressure > 100 mm Hg. A second blood pressure reading may be obtained by study personnel to assure blood pressure accuracy.
     • radiographic studies consistent with adult respiratory distress syndrome
     • Patients requiring acute dialysis
     • hyperferritinemia as defined by ferritin > 2000 ng/mL 55
     • Concurrent treatment with >5 mg of prednisone daily (or equivalent).

• Current or ongoing administration of calcineurin inhibitors, chemotherapy, radiation, or other immunosuppressive agents.

  • That cannot be held for 14 days after CTL infusion
  • That would not decay 3 1/2 half-lives by the day of CTL infusion using longest published half-life.

• Receipt of agents with ongoing immunosuppressive properties in the last 30 days including, ATG, Alemtuzumab, or similar agents.

• Prior allogeneic bone marrow, stem cell, or solid organ transplant. Patients with a history of autologous transplant are eligible for study if one year has elapsed since their transplant.

• Active HIV infection with CD4 count less than 200/ul.

• Pregnancy (lactating females allowable)

• Concomitant treatment with another experimental intervention for COVID-19 other than Remdesivir.

• History of allergic reaction to cellular therapy products (includes blood transfusion), diphenhydramine, or tocilizumb

• Corrected QT interval > 450 milliseconds

• History of torsade de pointes or other ventricular arrhythmia Women of childbearing potential, and partners of women of childbearing potential should be using at least one method of highly effective contraception at the time of enrollment and for the 14-day duration of the study.