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 .

Hyaline cartilage next generation implants from adipose-tissue-derived mesenchymal stem cells: Comparative study on 3D-printed polycaprolactone scaffold patterns.

We used additive manufacturing to fabricate 3D-printed polycaprolactone scaffolds of different geometry topologies and porosities. We present a comparative analysis of hyaline cartilage development from adipose-tissue-derived mesenchymal stem cells (ADMSCs) on three different, newly designed scaffold geometry patterns. The first scaffold design (MESO) was based on a rectilinear layer pattern. For the second pattern (RO45), we employed a 45° rotational layer loop. The design for the third scaffold (3DHC) was a three-dimensional honeycomb-like pattern with a hexagonal cellular distribution and small square shapes. We examined cell proliferation, colonization, and differentiation, in relation to the scaffold's structure, as well as to the mechanical properties of the final constructs. We gave emphasis on the scaffolds, both microarchitecture and macroarchitecture, for optimal and enhanced chondrogenic differentiation, as an important parameter, not well studied in the literature. Among the three patterns tested, RO45 was the most favourable for chondrogenic differentiation, whereas 3DHC better supported cell proliferation and scaffold penetration, exhibiting also the highest rate of increase onto the mechanical properties of the final construct. We conclude that by choosing the optimal scaffold architecture, the resulting properties of our cartilaginous constructs can better approximate those of the physiological cartilage.

Increased levels of Helicobacter pylori IgG antibodies in aqueous humor of patients with primary open-angle and exfoliation glaucoma.

PURPOSE: A prospective, nonrandomized, comparative study was carried out to investigate the levels of anti- H. pylori-specific IgG antibodies in the aqueous humor and serum of patients with primary open-angle glaucoma (POAG) and patients with exfoliation glaucoma (XFG), and to compare them with those in age-matched cataract patients. METHODS: Aqueous humor was aspirated at the beginning of glaucoma surgery from 26 eyes of 26 patients with POAG, 27 eyes of 27 patients with XFG, and at the beginning of phakoemulsification cataract surgery from 31 eyes of 31 age-matched normotensive cataract patients. Serum samples were obtained the day before surgery from all patients. Anti- H. pylori IgG concentration in the aqueous humor and serum was measured by means of an enzyme-linked immunosorbent assay. RESULTS: The mean concentration (+/- SE) of anti- H. pylori-specific IgG was significantly greater in the aqueous humor samples from patients with POAG (14.27+/-3.86 U/ml) and XFG (14.25+/-3.39 U/ml) than in those from age-matched control cataract patients (4.67+/-1.07 U/ml); ( P=0.006 and P=0.003, respectively). No difference was observed in the levels of H. pylori-specific IgG antibodies between POAG and XFG aqueous humor samples ( P=0.5). Similarly, the serum concentration of anti- H. pylori antibodies was significantly greater in patients with POAG (69.96+/-9.69 U/ml; P=0.013) and XFG (81.37+/-10.62 U/ml; P=0.002) than in the cataract controls (44.16+/-6.48 U/ml). The mean vertical cupping correlated significantly with the titer of anti- H. pylori-specific IgG in the aqueous humor in the POAG patients. CONCLUSION: H. pylori-specific IgG antibody levels are significantly increased in the aqueous humor and serum of patients with POAG and XFG. Moreover, the titer of anti- H. pylori antibody in the aqueous humor might reflect the severity of glaucomatous damage in POAG patients. These findings support a role for H. pylori infection in the pathobiology of these two common glaucomas.