In this phase I/II trial natural killer (NK) cells or memory T lymphocytes will be infused from donors who have recovered from COVID-19 and have complete resolution of symptoms for at least 14 days.~There will be two arms based on the biology of the donor and the patient:~Arm 1. Infusion of memory T cells from HLA partially match donors which have the SARS-COV-2 memory T cell repertoire.~Arm 2. Infusion of NK cells which are cells of the innate immune system that can eliminate virally infected cells.~The investigators expect a quick recovery of the patients with pneumonia or lymphopenia for two reasons:~The pool of memory T cells will increase in patients. Memory T cell levels are low in these patients. These lymphocytes have long-life memory, which upon reencountering SARS-CoV-2 will induce enhanced effector function resulting in greater protection of the patient.~NK cells act quickly after a viral infection. The number and function of NK cells correlates with the severity of another coronavirus infection, Severe Acute Respiratory Syndrome (SARS), originated in China in 2002.~Moreover, the investigators have previous successful experience with other viruses such as CMV, EBV and HHV-6.~Patients who have recovered from COVID-19 are the ideal donor candidates because they have immune cells with memory against SARS-CoV-2. Therefore, the infusion of NK and memory T cells from these donors will increase the pool of cells with cytotoxicity to virally infected cells, and will increase the pool of memory cells that respond quicker to a previously encountered stimulus.~This will impact in saving thousands of lives, releasing hospital beds, reducing the costs of a national health system and improving the economy of a locked-down country.~Cell therapies are safe and cost-effective and successfully used in other diseases. The investigators need new innovative treatments where others have failed.~We have performed the phase I:~Arm 1.Phase I single-center dose-escalation in 9 patients infused with memory T cells from a HLA partially match convalescent donor.~Arm 2. Phase I single-center dose-escalation in 6 patients infused with NK cells from convalescent donors.~We evaluate the safety, and feasibility, and obtained the RP2D of a single infusion.~We have performed the phase II with memory T cells:~The phase II for the infusion of memory T cells from HLA partially match convalescent donors has been carried out. 84 patients have been enrolled and randomized into the SoC treatment or the SoC plus the infusion of memory T cells.
This is a phase I/II clinical trial using adoptive cell therapy with NK cells or memory T cells in patients affected by COVID-19.~Severe cases with COVID-19 present a dysregulated immune system with T cell lymphopenia, specially NK cells and memory T cells, and a hyper-inflammatory state.~This clinical trial proposes the use of cell therapy for the treatment of patients with worse prognosis due to SARS-CoV-2 infection (those with pneumonia and/or lymphopenia). This is an innovative and a non-pharmacological intervention.