T CELL THERAPY OPPOSING NOVEL COVID-19 INFECTION IN IMMUNOCOMPROMISED PATIENTS

Eligibility Criteria

• 1. For receipt of CSTs derived from an HSCT donor under Arm A:
• 2. For receipt of CSTs derived from an HSCT donor under Arm B:
• 3. Have evidence of primary engraftment following HSCT (defined by ANC ≥500/mm3 for three consecutive measurements on different days, respectively)
• 4. Participants receiving steroids for treatment of GVHD or for other reasons, dosage must have been tapered to \<0.5 mg/kg/day of prednisone (or equivalent) at least 7 days prior to infusion.
• 5. Karnofsky/Lansky score \>70.
• 6. ≥12 years to \<80 years of age at enrollment.
• 7. Absolute neutrophil count (ANC) ≥500/ul.
• 8. Hemoglobin ≥8.0g/dl (level can be achieved with transfusion).
• 9. Platelets ≥20 K/ul (level can be achieved with transfusion) \*.
• 10. Bilirubin ≤2x upper limit normal.
• 11. Aspartate transaminase (AST) ≤2.5x upper limit of normal.
• 12. Alanine transaminase (ALT) ≤2.5x upper limit of normal.
• 13. Cystatin C with estimated GFR \>60mL/min/1.73m2 (calculated via the CKD-EPI 2012 equation).
• 14. Pulse oximetry of ≥92% on room air for at least 7 days prior to infusion.
• 15. Age appropriate mean arterial pressure without the use of vasopressors.
• 16. Negative pregnancy test in female participant of childbearing age.
• 17. Male and female participants of childbearing age must use highly effective birth control measures or practice abstinence for a minimum of 6 months after receiving study therapy.
• 18. Written informed consent and/or signed assent line from participant, parent or guardian.
• 1. Participants receiving biological or immunosuppressive monoclonal antibodies targeting T cells within 28 days prior to CST infusion, including ATG, Alemtuzumab, Basiliximab, Tociluzimab, Brentuximab, or other medications under this category as determined by the investigators.
• 2. Participants who have received donor lymphocyte infusion (DLI), chimeric antigen receptor T cell infusion, or other experimental cellular therapies within 28 days prior to CST infusion.
• 3. Participants who have received ruxolitinib or other JAK inhibitors within 7 days prior to CST infusion.
• 4. Participants with uncontrolled or progressing infections or active infections causing fever (temperature ≥38.1°C). Uncontrolled infections are defined as bacterial, fungal, or viral infections (including HIV and Hep B and C) with either clinical signs of worsening despite standard therapy that may be attributed to the uncontrolled infection. Progressing infection is defined as hemodynamic instability, worsening physical signs, or radiographic findings attributable to infection.
• 1. For bacterial infections, participants must be receiving definitive therapy and have no signs of progressing infection within 7 days prior to CST infusion.
• 2. For fungal infections, participants must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection within 7 days prior to CST infusion.
• 5. Participants with unexplained fever (temperature ≥38.1°C) within 7 days prior to CST infusion.
• 6. Participants with evidence of active SARS-CoV-2 infection based on SARS-CoV-2 RT-PCR positivity.
• 7. Participants with fever (temperature ≥38.1°C) in the past 7 days.
• 8. Participants with hypotension (systolic blood pressure \<90 mmHg or mean arterial blood pressure \<55 mmHg in participants \<14 years of age or \<60 mmHg in participants ≥14 years of age).
• 9. Participants with pulse pressure \>40 mmHg.
• 10. Participants with respiratory rate \>20 breaths per minute.
• 11. Participants with heart rate ≥120 beats per minute.
• 12. Participants with uncontrolled hypertension as defined by systolic blood pressure \>99th percentile for age (children \<18 years), and systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥80 mmHg (participants ≥18 years).
• 13. Participants with metabolic instability.
• 14. Pediatric participants with modified Ross heart failure Class II disease and adult participants with NYHA Class II disease.
• 15. Participants with advanced pulmonary disease as defined by requirement for supplemental oxygen or positive pressure ventilation due to pulmonary disease. (This includes participants with active interstitial lung disease (ILD)/pneumonitis, advanced pulmonary disease, a history of ILD/pneumonitis requiring treatment with systemic steroids or a baseline oxygen requirement).
• 16. Participants with neurological or psychiatric disorders that would, in the opinion of the investigators, place them at increased risk of harm, impact the investigator's abilities to screen for adverse events in the subject, or impair the subject's ability to provide informed consent.
• 17. Participants receiving checkpoint inhibitors within the previous 3 months prior to CST infusion, including nivolumimab, pembroluzimab, or other related medications.
• 18. Participants with proven or suspected MIS (in both adults and children) based on the CDC definition and investigator judgement.
• 19. Participants who are breastfeeding.
• 20. Participants who have received live vaccines within 30 days, or any SARS-CoV-2 vaccine in the past 28 days prior to enrollment.
• 21. Participants with any other unrelated medical conditions that would impact the participant's safety in the opinions of the investigators.
• 22. Participants anticipated to need a blood transfusion within 48 hours of CST infusion.
• 23. Participants unwilling to utilize effective contraception during the study period (if applicable)