Robust and prototypical immune responses toward COVID-19 vaccine in First Nations peoples are impacted by comorbidities.

High-risk groups, including Indigenous people, are at risk of severe COVID-19. Here we found that Australian First Nations peoples elicit effective immune responses to COVID-19 BNT162b2 vaccination, including neutralizing antibodies, receptor-binding domain (RBD) antibodies, SARS-CoV-2 spike-specific B cells, and CD4+ and CD8+ T cells. In First Nations participants, RBD IgG antibody titers were correlated with body mass index and negatively correlated with age. Reduced RBD antibodies, spike-specific B cells and follicular helper T cells were found in vaccinated participants with chronic conditions (diabetes, renal disease) and were strongly associated with altered glycosylation of IgG and increased interleukin-18 levels in the plasma. These immune perturbations were also found in non-Indigenous people with comorbidities, indicating that they were related to comorbidities rather than ethnicity. However, our study is of a great importance to First Nations peoples who have disproportionate rates of chronic comorbidities and provides evidence of robust immune responses after COVID-19 vaccination in Indigenous people.

Progress in Respiratory Gene Therapy.

The prospect of gene therapy for inherited and acquired respiratory disease has energized the research community since the 1980s, with cystic fibrosis, as a monogenic disorder, driving early efforts to develop effective strategies. The fact that there are still no approved gene therapy products for the lung, despite many early phase clinical trials, illustrates the scale of the challenge: In the 1990s, first-generation non-viral and viral vector systems demonstrated proof-of-concept but low efficacy. Since then, there has been steady progress toward improved vectors with the capacity to overcome at least some of the formidable barriers presented by the lung. In addition, the inclusion of features such as codon optimization and promoters providing long-term expression have improved the expression characteristics of therapeutic transgenes. Early approaches were based on gene addition, where a new DNA copy of a gene is introduced to complement a genetic mutation: however, the advent of RNA-based products that can directly express a therapeutic protein or manipulate gene expression, together with the expanding range of tools for gene editing, has stimulated the development of alternative approaches. This review discusses the range of vector systems being evaluated for lung delivery; the variety of cargoes they deliver, including DNA, antisense oligonucleotides, messenger RNA (mRNA), small interfering RNA (siRNA), and peptide nucleic acids; and exemplifies progress in selected respiratory disease indications.

Using mobile phones, WhatsApp and phone interviews to explore how children's hospice nurses manage long-term relationships with parents: a feasibility pilot.

BACKGROUND: Mobile phones are familiar to most nurses, but the applications available for voice recording and transfer of audio files in research may not be. AIM: To provide an overview of a pilot study which trialled the use of mobile phones, WhatsApp and phone interviews as a safe and reliable means of collecting data. DISCUSSION: A pilot study was designed to test the use of: mobile phones as a safe and reliable way to record audio diaries as research data; WhatsApp to transmit the audio files; and phone interviews to explore them. Undertaking the pilot demonstrated that the tools proposed for collecting data were useable and acceptable to the target population and that the researcher's guidance for doing so was satisfactory. CONCLUSION: New technologies enable innovation but trialling them for useability is important. Confidentiality and consent need to be carefully managed when using WhatsApp to ensure a study is compliant with data protection regulations. IMPLICATIONS FOR PRACTICE: Collection of research data digitally and remotely has become increasingly mainstream and relied on during the COVID 19 pandemic. The methods discussed in this article provide solutions for timely data collection that are particularly useful when the researcher is geographically distant from participants. The 'in the moment' reflective nature of the audio diaries could also be applicable to non-research settings - for example, as a method of assisting ongoing professional development and/or collection of reflective accounts.

Large scale clinical trials: lessons from the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has presented substantial new challenges to clinical and research teams. Our objective was to analyse the experience of investigators and research delivery staff regarding the research response to COVID-19 in order to identify these challenges as well as solutions for future pandemic planning. METHODS: We conducted a survey of diverse research staff involved in delivery of COVID-19 clinical trials across the UK. This was delivered online across centres linked to the NIHR Respiratory Translational Research Collaboration. Responses were analysed using a formal thematic analysis approach to identify common themes and recommendations. RESULTS: 83 survey participants from ten teaching hospitals provided 922 individual question responses. Respondents were involved in a range of research delivery roles but the largest cohort (60%) was study investigators. A wide range of research experiences were captured, including early and late phase trials. Responses were coded into overarching themes. Among common observations, complex protocols without adaptation to a pandemic were noted to have hampered recruitment. Recommendations included the need to develop and test pandemic-specific protocols, and make use of innovations in information technology. Research competition needs to be avoided and drug selection processes should be explicitly transparent. CONCLUSIONS: Delivery of clinical trials, particularly earlier phase trials, in a pandemic clinical environment is highly challenging, and was reactive rather than anticipatory. Future pandemic studies should be designed and tested in advance, making use of pragmatic study designs as far as possible and planning for integration between early and later phase trials and regulatory frameworks.

T Cell Epitope Discovery in the Context of Distinct and Unique Indigenous HLA Profiles.

CD8+ T cells are a pivotal part of the immune response to viruses, playing a key role in disease outcome and providing long-lasting immunity to conserved pathogen epitopes. Understanding CD8+ T cell immunity in humans is complex due to CD8+ T cell restriction by highly polymorphic Human Leukocyte Antigen (HLA) proteins, requiring T cell epitopes to be defined for different HLA allotypes across different ethnicities. Here we evaluate strategies that have been developed to facilitate epitope identification and study immunogenic T cell responses. We describe an immunopeptidomics approach to sequence HLA-bound peptides presented on virus-infected cells by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Using antigen presenting cell lines that stably express the HLA alleles characteristic of Indigenous Australians, this approach has been successfully used to comprehensively identify influenza-specific CD8+ T cell epitopes restricted by HLA allotypes predominant in Indigenous Australians, including HLA-A*24:02 and HLA-A*11:01. This is an essential step in ensuring high vaccine coverage and efficacy in Indigenous populations globally, known to be at high risk from influenza disease and other respiratory infections.

Repatriation of a Critically Ill Coronavirus Disease 2019-Positive Patient Across Closed Borders.

We report on the international retrieval of a critically ill, ventilated, coronavirus disease 2019-positive patient from Dili, East Timor, into the intensive care unit of the Royal Darwin Hospital in Australia. The patient had severe respiratory failure, and the medical team in Dili was struggling to maintain adequate oxygenation with a fraction of inspired oxygen of 1 most of the time. This occurred during an outbreak of coronavirus disease 2019 in East Timor, placing strain on the local health system. Therefore, it was decided to transfer the patient to Australia. Given the closed international borders of Australia, organization of the retrieval and infection control measures were challenging and are described in the article. We discuss the need for a pathway to retrieve critically ill patients into a well-resourced country during a pandemic and the importance of public health measures including a robust vaccination program.

Genomic Evidence of In-Flight SARS-CoV-2 Transmission, India to Australia, April 2021.

Epidemiologic and genomic investigation of SARS-CoV-2 infections associated with 2 repatriation flights from India to Australia in April 2021 indicated that 4 passengers transmitted SARS-CoV-2 to >11 other passengers. Results suggest transmission despite mandatory mask use and predeparture testing. For subsequent flights, predeparture quarantine and expanded predeparture testing were implemented.

Evaluating apheresis platelets at reduced dose as a contingency measure for extreme shortages.

BACKGROUND: The COVID19 pandemic highlights the need for contingency planning in the event of blood shortages. To increase platelet supply, we assessed the operational impact and effect on platelet quality of splitting units prior to storage. STUDY DESIGN AND METHODS: Using production figures, we modeled the impact on unit numbers, platelet counts, and volumes of splitting only apheresis double donations into three units (yielding ⅔ doses), or all standard dose units in half. To assess quality, eight pools of three ABO/Rh-matched apheresis (Trima Accel) double donations in plasma were split to ⅔ and ½ volumes in both Terumo and Fresenius storage bags. These were irradiated and subject to maximal permitted periods of nonagitation (3 × 8 h) before comparing platelet quality markers (including pH, CD62P expression) to Day 9 of storage. RESULTS: Splitting all double donations into three predicted inventory expansion of 23% overall whereas halving all standard dose units clearly doubles stock. In our study, ⅔ and ½ doses contained 153 ± 15 × 109 (~138 ml) and 113 ± 11 × 109 (~102 ml) platelets respectively. Following storage, higher pH was observed in ⅔ than in ½ doses and in Terumo compared to Fresenius bags. The higher pH was reflected in better quality markers, including lower CD62P expression. Despite the differences, on Day 8 (of pH monitoring at expiry) all ⅔ doses and most ½ doses were ≥pH 6.4. CONCLUSION: A strategy to split apheresis platelets in plasma to lower doses is feasible, maintains acceptable platelet quality, and should be considered by blood services in response to extreme shortages.