generation of sars-cov-2-specific t lymphocytes from recovered donors and administration to high-risk covid-19 patients

Conditions: Severe COVID-19

Summary: open-label phase i (single-center)/ phase ii (multicenter) with randomization 2:1

phase i (single-center): the investigators will administer cov-2-sts in a dose escalation regimen of 2 dose levels (dl1: 1,5x10\^7 cov-2-sts in total; dl2: 2x10\^7 cov-2-sts/m\^2). 3 patients will be treated at each dose level (traditional 3+3 design) following by a 12-day wait period to assess safety of the infusions prior to escalating the next dose level (maximum 12 patients). the maximum tolerated dose will be determined phase ii (multicenter): randomization 2:1, 60 patients will receive the standard of care (soc) plus cov-2-sts (arm a) at the optimum dose which will be determined in phase i and 30 patients will receive only soc (arm β) phase ii (multicenter, extension): randomization 2:1, 53 patients will be enrolled in arm a to receive soc and up to two doses of cov-2-sts and 27 patients will receive only soc. randomization: patients who meet the eligibility criteria after signing the informed consent form they will randomly be assigned at 2:1 ratio to each of the 2 treatment groups. patients assigned to arm a will be hla-typed for hla-a, b and drb1 within 24h, and a suitable for them t cell product will be selected from the cell bank. if a suitable product is found, they will continue to arm a, otherwise, they will be assigned to arm b. objectives: i) to determine the feasibility of establishing a bank with gmp-compliant generated sars-cov-2 specific t-cells (cov-2-sts), well-characterized in terms of specificity, phenotype and expression of human leucocyte antigens (hla), which will be produced by 30 covid-19 recovered donors with broad hla diversity in order to be suitable for administration to at least 90 covid-19 patients ii) to determine the safety of cov-2-st administration as cellular immunotherapy in covid-19 patients, who meet specific inclusion criteria iii) to determine the efficacy of cov-2-st administration as cellular immunotherapy in covid-19 patients, who meet specific inclusion criteria

Eligibility criteria:
inclusion criteria: hospitalized patients, sars-cov-2 pcr positive, within 8 days from the onset of the symptoms (immunosuppressed patients are excluded from the time limit when they become chronic carriers of the virus), who have: * pneumonia or/and sato2 ≤94% on room air or/and respiratory rate ≥24breaths/min and * lymphopenia cd3+≤650/μl or/and alc≤1000/microl and * increased values of d-dimers (≥2χ) or/and ferritin (\>1000ng/ml) or/and crp (≥3χ) or/and ldh (≥2χ) exclusion criteria: * age ≤18 and ≥80 years old * onset of symptoms \>8 days (immunosuppressed patients are excluded from the time limit when they become chronic carriers of the virus) * corticosteroid administration at a dose of \>0.75mg/kg (methylprednisolone equivalent) * multiple organ failure * ards (acute respiratory distress syndrome) * mechanical ventilation * patients who received atg, or campath, or other t-cell-suppressing monoclonal antibody within 28 days prior to admission * patients with concomitant confirmed infection from another pathogen or with very high procalcitonin (pct) that may indicate additional infection * enrollment in another clinical trial * pregnancy * inability to sign informed consent form * judged ineligible by at the treating physician (treating physician's discretion) * bilirubin ≥2x of upper normal limit * ast ≥ 2x of upper normal limit * creatinine ≥ 2x of upper normal limit or with dialysis/hemodialysis needs * karnofsky score ≤50

Keywords: covid-19 virus-specific t cells sars-cov-2 coronavirus-specific t cells 2021-001022-22