SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Policy Statement: Towards better health for refugee children and young people in Australia and New Zealand: The RACP Perspective

Children and young people make up around 50% of the humanitarian refugee intake in Australia and New Zealand (over 13 000 people per year) and are arguably the most vulnerable subgroup. The health needs of refugee children and young people have been well documented and include high rates of preventable conditions and psychosocial morbidity. The primary aim of this policy statement is to advocate for timely and high quality health care for every refugee child and young person living in Australia and New Zealand. It recommends that the following are required in order to deliver the most effective health care to refugee children and young people: (i) health service enhancement, (ii) the promotion of research and the development of an evidence base, (iii) dedicated training, and (iv) professional practice. The recommendations range from interventions that involve government leadership to interventions directed at health services and professionals

Pre-emptive infiltration of levobupivacaine is superior to at-closure administration in lumbar laminectomy patients

This is a prospective, randomized, controlled trial that compared the efficacy of different protocols of local tissue infiltration with levobupivacaine or levobupivacaine-methylprednisolone at the surgical site for pain relief after lumbar discectomy. The objective of the study was to determine the efficacy of preemptive wound infiltration with levobupivacaine and levobupivacaine-methylprednisolone at the surgical site for pain relief. Patients usually suffer significant pain after lumbar discectomy. Wound infiltration with local anesthetics with or without corticosteroids is one method to address this. A total of 100 patients were randomly allocated to five equal groups as follows: Group I had the musculus multifidi near the operated level infiltrated with 30 mL 0.25% levobupivacaine and 40 mg methylprednisolone just before wound closure; Group II had the same region infiltrated with 30 mL 0.25% levobupivacaine alone before closure; Group III had this region infiltrated with 30 mL 0.25% levobupivacaine and 40 mg methylprednisolone before the incision was made; in Group IV this region was infiltrated with 30 mL 0.25% levobupivacaine alone before incision; and in Group C (controls) this region was infiltrated with 30 mL 0.9% NaCl just before wound closure. Demographics, vital signs, postoperative pain scores and morphine usage were recorded. All four treatment groups showed significantly better results than the control group for most parameters. The treated groups had lower parenteral opioid requirements after surgery, lower incidences of nausea and shorter hospital stays. Further, the data indicate that, compared with infiltration of these drugs at wound closure, preemptive injection of levobupivacaine or levobupivacaine-methylprednisolone into the muscle near the operative site provides more effective analgesia after lumbar discectomy. Our data suggest that preemptive infiltration of the wound site with levobupivacaine alone or combined with methylprednisolone provides effective pain control with reduced opiate dose after unilateral lumbar discectomy