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We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-g and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A*01:01-restricted CD8+ ORF3a epitope FTSDYYQLY 207-215 ; due to P13L, P13S, and P13T in the B*27:05-restricted CD8+ nucleocapsid epitope QRNAP-RITF 9-17 ; and due to T362I and P365S in the A*03:01/A*11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK 361-369 . CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.

Successful viral infection involves a series of interactions between the virus and the host cell. The outcome of viral infection is, in fact, dependent on intact cellular function; it is required for viral binding, internalization, and uncoating. To determine the potential importance of lysosomal processing on the outcome of infection with a nonenveloped virus, we have studied the effects of NILCI on the course of reovirus infection on a beta-cell tumor in culture.Addition of 10 mM NH4CI to the medium inhibited viral growth by >80% and reduced toxic effects of the virus on cell viability, protein, and DNA synthesis by 3045%. In addition, synthesis of viral proteins was markedly decreased. Uptake of virus preiabeled with V35Simethionine was not affected by the ammonium; however, cleavage of ,ulC, an outer capsid protein of the virus wliose cleavage appears to be required for viral replication, was delayed. These results suggest that intracellular processing of reovirus is dependent on a lysosomal pathway and that disruption of this pathway can alter the course of viral infection.

Purpose Whilst there is a growing body of research which discusses the use of remotely piloted aircraft systems (RPAS) (otherwise known as “drones”) to transport medical supplies, almost all reported cases employ short range aircraft. The purpose of this paper is to consider the advantages and challenges inherent in the use of long endurance remotely piloted aircraft systems (LE-RPAS) aircraft to support the provision of medical supplies to remote locations – specifically “medical maggots” used in maggot debridement therapy (MDT) wound care. Design/methodology/approach After introducing both MDT and the LE-RPAS technology, the paper first reports on the outcomes of a case study involving 11 semi-structured interviews with individuals who either have experience and expertise in the use of LE-RPAS or in the provision of healthcare to remote communities in Western Australia. The insights gained from this case study are then synthesised to assess the feasibility of LE-RPAS assisted delivery of medical maggots to those living in such geographically challenging locations. Findings No insuperable challenges to the concept of using LE-RPAS to transport medical maggots were uncovered during this research – rather, those who contributed to the investigations from across the spectrum from operators to users, were highly supportive of the overall concept. Practical implications The paper offers an assessment of the feasibility of the use of LE-RPAS to transport medical maggots. In doing so, it highlights a number of infrastructure and organisational challenges that would need to be overcome to operationalise this concept. Whilst the particular context of the paper relates to the provision of medical support to a remote location of a developed country, the core benefits and challenges that are exposed relate equally to the use of LE-RPAS in a post-disaster response. To this end, the paper offers a high-level route map to support the implementation of the concept. Social implications The paper proposes a novel approach to the efficient and effective provision of medical care to remote Australian communities which, in particular, reduces the need to travel significant distances to obtain treatment. In doing so, it emphasises the importance in gaining acceptance of both the use of MDT and also the operation of RPAS noting that these have previously been employed in a military, as distinct from humanitarian, context. Originality/value The paper demonstrates how the use of LE-RPAS to support remote communities offers the potential to deliver healthcare at reduced cost compared to conventional approaches. The paper also underlines the potential benefits of the use of MDT to address the growing wound burdens in remote communities. Finally, the paper expands on the existing discussion of the use of RPAS to include its capability to act as the delivery mechanism for medical maggots.

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Background Since the emergence of SARS-CoV-2, evolutionary pressure has driven large increases in the transmissibility of the virus. However, with increasing levels of immunity through vaccination and natural infection the evolutionary pressure will switch towards immune escape. Genomic surveillance in regions of high immunity is crucial in detecting emerging variants that can more successfully navigate the immune landscape. Methods We present phylogenetic relationships and lineage dynamics within England (a country with high levels of immunity), as inferred from a random community sample of individuals who provided a self-administered throat and nose swab for rt-PCR testing as part of the REal-time Assessment of Community Transmission-1 (REACT-1) study. During round 14 (9 September–27 September 2021) and 15 (19 October–5 November 2021) lineages were determined for 1322 positive individuals, with 27.1% of those which reported their symptom status reporting no symptoms in the previous month. Results We identified 44 unique lineages, all of which were Delta or Delta sub-lineages, and found a reduction in their mutation rate over the study period. The proportion of the Delta sub-lineage AY.4.2 was increasing, with a reproduction number 15% (95% CI 8–23%) greater than the most prevalent lineage, AY.4. Further, AY.4.2 was less associated with the most predictive COVID-19 symptoms (p = 0.029) and had a reduced mutation rate (p = 0.050). Both AY.4.2 and AY.4 were found to be geographically clustered in September but this was no longer the case by late October/early November, with only the lineage AY.6 exhibiting clustering towards the South of England. Conclusions As SARS-CoV-2 moves towards endemicity and new variants emerge, genomic data obtained from random community samples can augment routine surveillance data without the potential biases introduced due to higher sampling rates of symptomatic individuals.

Intake of added sugars during early life is associated with poor health outcomes. Maternal dietary intake influences the intake of their children, but little research investigates the relationship between maternal sugar sweetened beverage (SSB) and infant/toddler added sugar intakes. Our objective was to explore the relationship between maternal total sugars and SSB intakes and infant/toddler added sugar intakes. This cross-sectional study (n = 101) of mother-infant dyads measured maternal dietary intake by food frequency questionnaire and infant intake by three 24-h dietary recalls. Pearson’s correlations explored the relations between maternal total sugars and SSB intakes and infant added sugar intakes. Hierarchical stepwise regressions determined if maternal total sugars and SSB intakes explained the variation in infant added sugar intakes after accounting for known risk factors for early introduction of added sugars. Maternal total sugars (r = 0.202, p = 0.043) and SSB (r = 0.352, p < 0.001) intakes were positively correlated with infant/toddler added sugar intakes. In the hierarchical models, maternal total sugar intakes did not account for more variance in infant added sugar intakes (β = 0.046, p = 0.060), but maternal SSB intake was a significant contributor of infant added sugar intakes (β = 0.010, p = 0.006) after accounting for confounders. Interventions to reduced maternal SSB consumption may help reduce infant/toddler added sugar intakes.

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