Background: Effective treatments are still needed to reduce the severity of symptoms, time of hospitalization, and mortality of COVID-19. SARS-CoV-2 specific memory T-lymphocytes obtained from convalescent donors recovered can be used as passive cell immunotherapy. Methods: Between September and November 2020 a phase 1, dose-escalation, single centre clinical trial was conducted to evaluate the safety and feasibility of the infusion of CD45RA À memory T cells containing SARS-CoV-2 specific T cells as adoptive cell therapy against moderate/severe cases of COVID-19. Nine participants with pneumonia and/or lymphopenia and with at least one human leukocyte antigen (HLA) match with the donor were infused. The first three subjects received the lowest dose (1 £ 10 5 cells/kg), the next three received the intermediate dose (5 £ 10 5 cells/kg) and the last three received the highest dose (1 £ 10 6 cells/ kg) of CD45RA À memory T cells. Clinicaltrials.gov registration: NCT04578210. Findings: All participants' clinical status measured by National Early Warning Score (NEWS) and 7-category point ordinal scales showed improvement six days after infusion. No serious adverse events were reported. Inflammatory parameters were stabilised post-infusion and the participants showed lymphocyte recovery two weeks after the procedure. Donor microchimerism was observed at least for three weeks after infusion in all patients. Interpretation: This study provides preliminary evidence supporting the idea that treatment of COVID-19 patients with moderate/severe symptoms using convalescent CD45RA À memory T cells is feasible and safe. Funding: Clinical Trial supported by Spanish Clinical Research Network PT17/0017/0013. Co-funded by European Regional Development Fund/European Social Fund. CRIS CANCER Foundation Grant to AP-M and Agencia Valenciana de Innovaci on Grant AVI-GVA COVID-19-68 to BS.
Pretransplantation sensitization against MICA and HLA are independent events. Preformed anti-MICA antibodies independently increase risk for kidney rejection and enhance the deleterious effect of PRA+ status early after transplantation.
Three dimensional interconnected macroporous (pore diameter: 600-800 μm) hydroxyapatite/agarose disks have been evaluated in this study as potential bone regeneration scaffolds. With this purpose, the adhesion and proliferation of human Saos-2 osteoblasts on this biomaterial were analyzed. As an index of cell function, the following parameters were measured: cell morphology, viability, cell size/complexity, cell cycle, reactive oxygen species (ROS) content, and lactate dehydrogenase (LDH) release. The existence of anoikis induced by inappropriate contacts between the cell and the scaffold has been detected by scanning electron microscopy, confocal microscopy, and flow cytometry. The intracellular nitric oxide content has been also measured as potential inducer of anoikis. The positive effects of previous scaffold coating with type I collagen on osteoblast adhesion as well as the collagen protection against anoikis have been demonstrated in this study.
Preformed anti-MICA antibodies may occasionally be cytotoxic by fixing and activating complement. This way they might contribute to worse early kidney graft function.
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