SARS-CoV-2-specific T cell therapy for severe COVID-19: a randomized phase 1/2 trial.

Despite advances, few therapeutics have shown efficacy in severe coronavirus disease 2019 (COVID-19). In a different context, virus-specific T cells have proven safe and effective. We conducted a randomized (2:1), open-label, phase 1/2 trial to evaluate the safety and efficacy of off-the-shelf, partially human leukocyte antigen (HLA)-matched, convalescent donor-derived severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cells (CoV-2-STs) in combination with standard of care (SoC) in patients with severe COVID-19 compared to SoC during Delta variant predominance. After a dose-escalated phase 1 safety study, 90 participants were randomized to receive CoV-2-ST+SoC (n = 60) or SoC only (n = 30). The co-primary objectives of the study were the composite of time to recovery and 30-d recovery rate and the in vivo expansion of CoV-2-STs in patients receiving CoV-2-ST+SoC over SoC. The key secondary objective was survival on day 60. CoV-2-ST+SoC treatment was safe and well tolerated. The study met the primary composite endpoint (CoV-2-ST+SoC versus SoC: recovery rate 65% versus 38%, P = 0.017; median recovery time 11 d versus not reached, P = 0.052, respectively; rate ratio for recovery 1.71 (95% confidence interval 1.03-2.83, P = 0.036)) and the co-primary objective of significant CoV-2-ST expansion compared to SοC (CoV-2-ST+SoC versus SoC, P = 0.047). Overall, in hospitalized patients with severe COVID-19, adoptive immunotherapy with CoV-2-STs was feasible and safe. Larger trials are needed to strengthen the preliminary evidence of clinical benefit in severe COVID-19. EudraCT identifier: 2021-001022-22 .

Biomimetic synthesis of ribbon-like hydroxyapatite employing poly(l-arginine).

Binding of a polypeptide on colloidal particles can affect the dissolution of mineral, initiate crystal nucleation and change the growth kinetics of the precipitated crystal. In this study the synthesis of hydroxyapatite nanocrystals was performed in the presence of poly(L-arginine), PA. Aqueous solutions of Ca(2+), phosphate, and PA were employed at calcium:PA molar ratios ranging from 2:1 to 1:2 and the resulting suspensions were hydrothermally treated at 80 °C for 16 h, or at 130 °C for 6h. The resulting nanomaterials were characterized by XRD, FTIR, TEM, SEM, and TGA. It was found that the presence of PA promotes HAP formation and affects its crystal size and morphology possibly through a rather specific interaction between the homopeptide that is positively charged and also that adopts a ß-sheet conformation and the negatively charged c-plane of the growing HAP crystal. In all cases, hexagonal HAP crystals with thin ribbon-like morphology were obtained. Increase of the PA ratio and of the hydrothermal temperature leads to more homogeneous and narrower size distributions with crystallites having widths ranging between 5 to 50 nm and lengths ranging from 50 to 450 nm.