Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report

The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. This unusual clinical course is consistent with a contribution of antibodies to both viral clearance and progression to severe disease. In the absence of these confounders, we take an experimental medicine approach to examine the in vivo utility of remdesivir. Over two independent courses of treatment, we observe a temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients

Animal welfare regulation in the Australian agricultural sector: a legitimacy maximising analysis

Theoretical thesis.Bibliography: pages 307-341.Part 1. Setting the regulatory scene. Chapter 1.Introduction ; Chapter 2. The nature of the regulatory problem : industrial livestock production and animal welfare ; Chapter 3. The nature of the regulatory problem II : the social and political context : a clash of values ; Chapter 4. The current regulatory framework ; Chapter 5. Overview of the regulatory failings -- Part 2. Investigation and critique. Chapter 6. Regulators, agency design and regulatory capture ; Chapter 7. Animal welfare standard-setting ; Chapter 8. Implementation and enforcement ; Chapter 9. Conclusions and recommendations for reform.Sociological research indicates that public values and attitudes towards animals are changing. Since the 1970s traditional instrumental conceptions of animals as things to be used for human benefit have been giving way to a post-material ethic of care and compassion. Such changes are materialising in increased public scrutiny of animal use industries. Recent controversies over the treatment of animals within Australia’s agricultural sector have raised questions over the adequacy of current governance and regulatory arrangements for farm animal welfare. In particular, concerns have been expressed over perceived conflicts of interest on behalf of state and federal departments of agriculture in administering animal welfare law.This thesis aims to provide analytical and empirical depth to such claims and to assess the broader democratic legitimacy of current governance structures for farm animal welfare in light of the changing societal ethic towards animals. The assessment takes place within the analytical frames of regulatory capture and legitimacy theories. Data from semi-structured interviews with regulators responsible for animal welfare in state, territory, and federal jurisdictions are analysed to provide further insight to the assessment.The research finds that the departments responsible for protecting farm animal welfare possess conflicting institutional objectives. This conflict materialises in the form of structural incentives to prioritise industry productivity goals over those of farm animal welfare. Key personnel responsible for the administration of farm animal welfare laws operate within an institutional setting that imposes significant limitations on what they can do to protect and promote the welfare of farmed animals. As a consequence, farm animal welfare is viewed in instrumental terms and valued only to the extent it contributes to industry productivity goals. This approach causes the regulators to deviate from serving the public interest underpinning the farm animal welfare regulatory framework by creating exclusionary standard-setting and enforcement processes that do not reflect the citizenry’s values or meet their normative expectations. Consequences for the framework’s legitimacy are then assessed before the thesis concludes with proposing a number of options for reform to create a more inclusive, fair, and democratic system of farm animal welfare governance.Mode of access: World wide web1 online resource (x, 341 pages) illustrations (some colour

A Critical Analysis of the British Horseracing Authority’s Review of the Use of the Whip in Horseracing

There is increasing controversy about the use of the whip as a performance aid in Thoroughbred horseracing and its impact on horse welfare. This paper offers a critical analysis of the British Horseracing Authority’s (BHA) 2011 Report Responsible Regulation: A Review of the Use of the Whip in Horseracing. It examines the BHA’s process of consultation and use of science and public opinion research through the application of current scientific literature and legal analysis. This analysis suggests that the BHA’s findings on the welfare impact and justification for whip use are insufficiently defended by the report. These findings indicate that the report is an inadequate basis from which to draw any definitive conclusions on the impact of whips on racehorse welfare. Further review is needed, undertaken by an independent scientific body, to advance this debate

Longitudinal analysis reveals that delayed bystander CD8+ T cell activation and early immune pathology distinguish severe COVID-19 from mild disease

The kinetics of the immune changes in COVID-19 across severity groups have not been rigorously assessed. Using immunophenotyping, RNA sequencing, and serum cytokine analysis, we analyzed serial samples from 207 SARS-CoV2-infected individuals with a range of disease severities over 12 weeks from symptom onset. An early robust bystander CD8+ T cell immune response, without systemic inflammation, characterized asymptomatic or mild disease. Hospitalized individuals had delayed bystander responses and systemic inflammation that was already evident near symptom onset, indicating that immunopathology may be inevitable in some individuals. Viral load did not correlate with this early pathological response but did correlate with subsequent disease severity. Immune recovery is complex, with profound persistent cellular abnormalities in severe disease correlating with altered inflammatory responses, with signatures associated with increased oxidative phosphorylation replacing those driven by cytokines tumor necrosis factor (TNF) and interleukin (IL)-6. These late immunometabolic and immune defects may have clinical implications