No abstract

Until vaccines and effective therapeutics become available, the practical solution to transit safely out of the current coronavirus disease 19 (CoVID-19) lockdown may include the implementation of an effective testing, tracing and tracking system. However, this requires a reliable and clinically validated diagnostic platform for the sensitive and specific identification of SARS-CoV-2. Here, we report on the development of a de novo, high-resolution and comparative genomics guided reverse-transcribed loop-mediated isothermal amplification (LAMP) assay. To further enhance the assay performance and to remove any subjectivity associated with operator interpretation of results, we engineered a novel hand-held smart diagnostic device. The robust diagnostic device was further furnished with automated image acquisition and processing algorithms and the collated data was processed through artificial intelligence (AI) pipelines to further reduce the assay run time and the subjectivity of the colorimetric LAMP detection. This advanced AI algorithm-implemented LAMP (ai-LAMP) assay, targeting the RNA-dependent RNA polymerase gene, showed high analytical sensitivity and specificity for SARS-CoV-2. A total of ~200 coronavirus disease (CoVID-19)-suspected NHS patient samples were tested using the platform and it was shown to be reliable, highly specific and significantly more sensitive than the current gold standard qRT-PCR. Therefore, this system could provide an efficient and cost-effective platform to detect SARS-CoV-2 in resource-limited laboratories.

Interferons are an essential component of the innate arm of the immune system and are arguably one of the most important lines of defence against viruses. The human IFN system and its functionality has already been largely characterized and studied in detail. However, the IFN systems of bats have only been marginally examined to date up until the recent developments of the Bat1k project which have now opened new opportunities in research by identifying six new bat genomes to possess novel genes that are likely associated with viral tolerance exhibited in bats. Interestingly, bats have been hypothesized to possess the ability to establish a host-virus relationship where despite being infected, they exhibit limited signs of disease and still retain the ability to transmit the disease into other susceptible hosts. Bats are one of the most abundant and widespread vertebrates on the planet and host many zoonotic viruses that are highly pathogenic to humans. Several genomics, immunological, and biological features are thought to underlie novel antiviral mechanisms of bats. This review aims to explore the bat IFN system and developments in its diverse IFN features, focusing mainly on the model species, the Australian black flying fox (Pteropus alecto), while also highlighting bat innate immunity as an exciting and fruitful area of research to understand their ability to control viral-mediated pathogenesis.

Background Until five years ago, the metastatic hormone-sensitive prostate cancer (mHSPC) treatment landscape was dominated by the use of androgen deprivation therapy (ADT) alone. However, novel hormonal agents (NHAs) and chemotherapy are now approved for male patients with mHSPC. This study aimed to understand the impact NHA approvals had on mHSPC real-world treatment patterns and to identify the key factors associated with NHA or chemotherapy (± ADT) usage vs ADT alone. Methods Data were collected from the Adelphi Prostate Cancer Disease Specific Programme (DSP)™, a point-in-time survey of physicians and their consulting patients conducted in the United States (US), five European countries (France, Germany, Italy, Spain, and the United Kingdom), and Japan between January and August 2020. Data were analysed using descriptive statistics for individual countries, regions, and all countries combined. Pairwise analyses were used to further investigate differences between treatment groups at global level. Results 336 physicians provided data on 1195 mHSPC patients. Globally, at data collection, the most common mHSPC regimen initiated first was ADT alone (47%), followed by NHAs (± ADT) (31%, of which 21% was abiraterone, 8% was enzalutamide, and 2% was apalutamide) and chemotherapy (± ADT) (19%). The highest rates of ADT alone usage were observed in Japan (78%) and Italy (66%), and the lowest in Spain (34%) and in the US (36%). Our results showed that clinical decision making was driven by patient fitness, compliance, tolerance of adverse events, and balance of impact on quality of life vs overall survival. Conclusions This real-world survey offered early insights into the evolving mHSPC treatment paradigm. It showed that in 2020, ADT alone remained the most common initial mHSPC therapy, suggesting that physicians may prefer using treatments which they are familiar and have experience with, despite clinical trial evidence of improved survival with NHAs or chemotherapy (± ADT) vs ADT alone. Results also indicated that physicians prescribed specific mHSPC treatments primarily based on the following criteria: patient preference, disease burden/severity, and the performance status and comorbidities of the patient. To fully appreciate the rapidly changing mHSPC treatment landscape and monitor NHA uptake, additional real-world studies are required.

The emergence of multiple variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the importance of possible animal-to-human (zoonotic) and human-to-animal (zooanthroponotic) transmission and potential spread within animal species. A range of animal species have been verified for SARS-CoV-2 susceptibility, either in vitro or in vivo. However, the molecular bases of such a broad host spectrum for the SARS-CoV-2 remains elusive. Here, we structurally and genetically analysed the interaction between the spike protein, with a particular focus on receptor binding domains (RBDs), of SARS-CoV-2 and its receptor angiotensin-converting enzyme 2 (ACE2) for all conceivably susceptible groups of animals to gauge the structural bases of the SARS-CoV-2 host spectrum. We describe our findings in the context of existing animal infection-based models to provide a foundation on the possible virus persistence in animals and their implications in the future eradication of COVID-19.

Until vaccines and effective therapeutics become available, the practical way to transit safely out of the current lockdown may include the implementation of an effective testing, tracing and tracking system. However, this requires a reliable and clinically validated diagnostic platform for the sensitive and specific identification of SARS-CoV-2. Here, we report on the development of a de novo, high-resolution and comparative genomics guided reverse-transcribed loop-mediated isothermal amplification (LAMP) assay. To further enhance the assay performance and to remove any subjectivity associated with operator interpretation of result, we engineered a novel hand-held smart diagnostic device. The robust diagnostic device was further furnished with automated image acquisition and processing algorithms, and the collated data was processed through artificial intelligence (AI) pipelines to further reduce the assay run time and the subjectivity of the colorimetric LAMP detection. This advanced AI algorithm-implemented LAMP (ai-LAMP) assay, targeting the RNA-dependent RNA polymerase gene, showed high analytical sensitivity and specificity for SARS-CoV-2. A total of ~200 coronavirus disease (CoVID-19)-suspected patient samples were tested using the platform and it was shown to be reliable, highly specific and significantly more sensitive than the current gold standard qRT-PCR. The system could provide an efficient and cost-effective platform to detect SARS-CoV-2 in resource-limited laboratories.

No abstract

5065 Background: Based on level 1 evidence of overall survival, ASCO/NCCN/AUA guidelines uniformly recommend novel hormonal therapy (NHT) or chemotherapy (CHT) added to androgen deprivation therapy (ADT) as standard of care in mCSPC. However, real-world evidence across US healthcare systems suggests most patients receive ADT +/- first generation non-steroidal antiandrogens (NSAA). Reasons behind the lack of treatment intensification (TI) in mCSPC have not been studied. Methods: Data from medical charts of patients initiating mCSPC treatment from Jul ’18-Nov ‘21 were retrospectively extracted from multiple US academic/community practices. Oncologists and urologists who treated these patients were surveyed to provide reasons for treatment choices including prostate specific antigen (PSA) goals and explicit reasons for not prescribing NHT. Descriptive statistics (Fishers exact tests) were used to compare outcomes between groups; p-values for odds ratios (OR) were generated via Wald test. Results: 65 oncologists and 42 urologists provided data on 621 patients. Median age at initial mCSPC treatment start was 68.0 years, 58% were White, 25% Black, 84% had de novo metastases, 30% had high-volume disease including 22% with visceral metastases, and 83% had ECOG PS score ≤1. In the first-line (1L) setting, most mCSPC patients received ADT±NSAA alone (69%), while TI rates with ADT+NHT (26%) or ADT+CHT (4%) were low. An additional 27% (n = 166/621) received subsequent TI while still castration-sensitive. According to the physician survey, the top 5 reasons why their patients did not receive initial NHT were perceptions about: drug tolerability (38%), lack of clinical trial evidence of overall survival improvement (31%), lack of reimbursement (26%), patient financial constraints (20%), and questions about sequencing NHTs earlier vs later in disease (21%). Regarding treatment goals for PSA response, physicians more frequently reported a relative (%) reduction than an absolute PSA reduction (85% vs 51%). Oncologists considered a median PSA reduction of 50% (IQR 25-75) adequate vs 75% (IQR 50-90) among urologists. Urologists had higher rates of TI at 1L and/or subsequent treatment in patients who were still castration-sensitive (p < 0.01). Physicians who aimed for deeper PSA reduction of 75-100% were more likely (OR = 1.63; p = 0.034) to provide TI in 1L compared with physicians with less aggressive PSA goals (0-49%). Conclusions: To our knowledge, this is the first study identifying reasons for underutilization of intensified treatment in mCSPC. While survey results suggest perceptions of tolerability and lack of efficacy and financial considerations affect NHT use, in practice, non-guideline driven PSA reduction goals are associated with low rates of TI. These results demonstrate the need for further medical education.