COVID-19 vaccine effectiveness against hospitalisation and death of people in clinical risk groups during the Delta variant period: English primary care network cohort study.

BACKGROUND: COVID-19 vaccines have been shown to be highly effective against hospitalisation and death following COVID-19 infection. COVID-19 vaccine effectiveness estimates against severe endpoints among individuals with clinical conditions that place them at increased risk of critical disease are limited. METHODS: We used English primary care medical record data from the Oxford-Royal College of General Practitioners Research and Surveillance Centre sentinel network (N > 18 million). Data were linked to the National Immunisation Management Service database, Second Generation Surveillance System for virology test data, Hospital Episode Statistics, and death registry data. We estimated adjusted vaccine effectiveness (aVE) against COVID-19 infection followed by hospitalisation and death among individuals in specific clinical risk groups using a cohort design during the delta-dominant period. We also report mortality statistics and results from our antibody surveillance in this population. FINDINGS: aVE against severe endpoints was high, 14-69d following a third dose aVE was 96.4% (95.1%-97.4%) and 97.9% (97.2%-98.4%) for clinically vulnerable people given a Vaxzevria and Comirnaty primary course respectively. Lower aVE was observed in the immunosuppressed group: 88.6% (79.1%-93.8%) and 91.9% (85.9%-95.4%) for Vaxzevria and Comirnaty respectively. Antibody levels were significantly lower among the immunosuppressed group than those not in this risk group across all vaccination types and doses. The standardised case fatality rate within 28 days of a positive test was 3.9/1000 in people not in risk groups, compared to 12.8/1000 in clinical risk groups. Waning aVE with time since 2nd dose was also demonstrated, for example, Comirnaty aVE against hospitalisation reduced from 96.0% (95.1-96.7%) 14-69days post-dose 2-82.9% (81.4-84.2%) 182days+ post-dose 2. INTERPRETATION: In all clinical risk groups high levels of vaccine effectiveness against severe endpoints were seen. Reduced vaccine effectiveness was noted among the immunosuppressed group

INTERFERON INHIBITS SYNAPTIC POTENTIATION IN RAT HIPPOCAMPUS

The effects of rat interferon (IFN) on the electrically-induced potentiation of the synaptic transmission were studied in rat hippocampal slices by using extracellular field potential recordings. The treatment with rat IFN (120 U/ml) reduced the size of short-term potentiation (STP) and suppressed long-term potentiation (LTP). These IFN-induced effects were dose-dependent in the range of 50-500 U/ml. In addition, IFN slightly attenuated the potentiation when applied during the maintenance of LTP. Basal synaptic transmission was affected by IFN at concentrations greater-than-or-equal-to 250 U/ml. Following an acute exposure to IFN (500-2000 U/ml), cultured embryonic neurones from rat hippocampus often exhibited an attenuation of N-methyl-D-aspartate-induced currents and a variation (increase or decrease) of voltage-activated Ca2+ current amplitude. A possible role of IFN as neuromodulator in mammalian brain during immune responses is discussed

Tumor-necrosis-factor alters synaptic transmission in rat hippocampal slices

The effects of human recombinant tumor necrosis factor (TNF-alpha) on the synaptic transmission were studied in rat hippocampal slices by using extracellular field potential recordings. Population spikes and/or excitatory postsynaptic potentials were extracellularly recorded in hippocampus CA1 region from stratum pyramidale and stratum radiatum, respectively, and synaptic transmission was examined in the Schaffer collateral/commissural-CA1 pathway. Basal neurotransmission slightly and promptly increased in slices acutely exposed to TNF-alpha (1-100 nM). Examination of the long-term potentiation (LTP) revealed that a brief treatment with the cytokine did not influence LTP, while a long-lasting application of TNF-alpha (50 min or more) inhibited LTP in a dose-dependent way in the range of 1-100 nM. A role for TNF-alpha as a peptide of immunological significance belonging to the family of brain neuromodulators is discussed

The performance of human periodontal ligament mesenchymal stem cells on xenogenic biomaterials

Mesenchymal stem cells from periodontal ligament (PDL-MSCs) hold great promise for bone regeneration. Most studies regarding the osteogenic differentiation of stem cells from periodontal tissue suggest that PDL cells may have many osteoblast-like properties, including the ability to form calcified nodules in vitro. This study investigated the morphological and histochemistry aspects of human PDL-MSCs, induced for osteogenic differentiation and seeded on a xenogenic porcine bone substitute in vitro, at different times of incubation. This biomaterial seems physically identical to human bone, and it has been reported to be osteoconductive. Our results indicated that the cells had a high affinity for the three-dimensional biomaterials; in fact, cellular proliferation and colonization was evident, and after 21 days the adherent cells started to detach themselves from the substrate, and at 30 days of incubation in differentiation medium, the cells completely lost the adhesion to the Petri's disk, englobing all bioparticles. In conclusion, the in vitro behaviour of PDL-MSCs and their relationship with three-dimensional scaffold biomaterials encourage in vivo investigations for their use in dental tissue regeneration