Lessons learned from developing a COVID-19 algorithm governance framework in Aotearoa New Zealand

Aotearoa New Zealand's response to the COVID-19 pandemic has included the use of algorithms that could aid decision making. Te Pokapū Hātepe o Aotearoa, the New Zealand Algorithm Hub, was established to evaluate and host COVID-19 related models and algorithms, and provide a central and secure infrastructure to support the country's pandemic response. A critical aspect of the Hub was the formation of an appropriate governance group to ensure that algorithms being deployed underwent cross-disciplinary scrutiny prior to being made available for quick and safe implementation. This framework necessarily canvassed a broad range of perspectives, including from data science, clinical, Māori, consumer, ethical, public health, privacy, legal and governmental perspectives. To our knowledge, this is the first implementation of national algorithm governance of this type, building upon broad local and global discussion of guidelines in recent years. This paper describes the experiences and lessons learned through this process from the perspective of governance group members, emphasising the role of robust governance processes in building a high-trust platform that enables rapid translation of algorithms from research to practice.

Laboratory diagnosed microbial infection in English UK Biobank participants in comparison to the general population.

Understanding the genetic and environmental risk factors for serious bacterial infections in ageing populations remains incomplete. Utilising the UK Biobank (UKB), a prospective cohort study of 500,000 adults aged 40-69 years at recruitment (2006-2010), can help address this. Partial implementation of such a system helped groups around the world make rapid progress understanding risk factors for SARS-CoV-2 infection and COVID-19, with insights appearing as early as May 2020. In principle, such approaches could also to be used for bacterial isolations. Here we report feasibility testing of linking an England-wide dataset of microbial reporting to UKB participants, to enable characterisation of microbial infections within the UKB Cohort. These records pertain mainly to bacterial isolations; SARS-CoV-2 isolations were not included. Microbiological infections occurring in patients in England, as recorded in the Public Health England second generation surveillance system (SGSS), were linked to UKB participants using pseudonymised identifiers. By January 2015, ascertainment of laboratory reports from UKB participants by SGSS was estimated at 98%. 4.5% of English UKB participants had a positive microbiological isolate in 2015. Half of UKB isolates came from 12 laboratories, and 70% from 21 laboratories. Incidence rate ratios for microbial isolation, which is indicative of serious infection, from the UKB cohort relative to the comparably aged general population ranged from 0.6 to 1, compatible with the previously described healthy participant bias in UKB. Data on microbial isolations can be linked to UKB participants from January 2015 onwards. This linked data would offer new opportunities for research into the role of bacterial agents on health and disease in middle to-old age.

Lessons learned from developing a COVID-19 algorithm governance framework in Aotearoa New Zealand

Aotearoa New Zealand’s response to the COVID-19 pandemic has included the use of algorithms that could aid decision making. Te Pokapū Hātepe o Aotearoa, the New Zealand Algorithm Hub, was established to evaluate and host COVID-19 related models and algorithms, and provide a central and secure infrastructure to support the country’s pandemic response. A critical aspect of the Hub was the formation of an appropriate governance group to ensure that algorithms being deployed underwent cross-disciplinary scrutiny prior to being made available for quick and safe implementation. This framework necessarily canvassed a broad range of perspectives, including from data science, clinical, Māori, consumer, ethical, public health, privacy, legal and governmental perspectives. To our knowledge, this is the first implementation of national algorithm governance of this type, building upon broad local and global discussion of guidelines in recent years. This paper describes the experiences and lessons learned through this process from the perspective of governance group members, emphasising the role of robust governance processes in building a high-trust platform that enables rapid translation of algorithms from research to practice. [ FROM AUTHOR] Copyright of Journal of the Royal Society of New Zealand is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Bisubstrate Inhibitors of Severe Acute Respiratory Syndrome Coronavirus-2 Nsp14 Methyltransferase.

Taking advantage of the uniquely constricted active site of SARS-CoV-2 Nsp14 methyltransferase, we have designed bisubstrate inhibitors interacting with the SAM and RNA substrate binding pockets. Our efforts have led to nanomolar inhibitors including compounds 3 and 10. As a prototypic inhibitor, compound 3 also has an excellent selectivity profile over a panel of human methyltransferases. Remarkably, C-nucleoside 10 exhibits high antiviral activity and low cytotoxicity, leading to a therapeutic index (CC50/EC50) greater than 139. Furthermore, a brief metabolic profiling of these two compounds suggests that they are less likely to suffer from major metabolic liabilities. Moreover, computational docking studies point to protein-ligand interactions that can be exploited to enhance inhibitory activity. In short, discovery of inhibitor 10 clearly demonstrates that potent and selective anti-SARS-CoV-2 activity can be achieved by targeting the Nsp14 methyltransferase. Therefore, the current work strongly supports the continued pursuit of Nsp14 methyltransferase inhibitors as COVID-19 therapeutics.

Bisubstate Inhibitors of Severe Acute Respiratory Syndrome Coronavirus-2 Nsp14 Methyltransferase

Taking advantage of the uniquely constricted active site of SARS-CoV-2 Nsp14 methyltransferase, we have designed bisubstrate inhibitors interacting with the SAM and RNA substrate binding pockets. Our efforts have led to nanomolar inhibitors including compounds 3 and 10. As a prototypic inhibitor, compound 3 also has an excellent selectivity profile over a panel of human methyltransferases. Remarkably, C-nucleoside 10 exhibits high antiviral activity and low cytotoxicity, leading to a therapeutic index (CC50/EC50) greater than 139. Furthermore, a brief metabolic profiling of these two compounds suggests that they are less likely to suffer from major metabolic liabilities. Moreover, computational docking studies point to protein–ligand interactions that can be exploited to enhance inhibitory activity. In short, discovery of inhibitor 10 clearly demonstrates that potent and selective anti-SARS-CoV-2 activity can be achieved by targeting the Nsp14 methyltransferase. Therefore, the current work strongly supports the continued pursuit of Nsp14 methyltransferase inhibitors as COVID-19 therapeutics.

Performance of Thermoplastic Extrusion, Germination, Fermentation, and Hydrolysis Techniques on Phenolic Compounds in Cereals and Pseudocereals.

Bioactive compounds, such as phenolic compounds, are phytochemicals found in significant amounts in cereals and pseudocereals and are usually evaluated by spectrophotometric (UV-VIS), HPLC, and LC-MS techniques. However, their bioavailability in grains is quite limited. This restriction on bioavailability and bioaccessibility occurs because they are in conjugated polymeric forms. Additionally, they can be linked through chemical esterification and etherification to macro components. Techniques such as thermoplastic extrusion, germination, fermentation, and hydrolysis have been widely studied to release phenolic compounds in favor of their bioavailability and bioaccessibility, minimizing the loss of these thermosensitive components during processing. The increased availability of phenolic compounds increases the antioxidant capacity and favor their documented health promoting.

Ocular transmissibility of COVID-19: possibilities and perspectives.

Since the initial outbreak of coronavirus disease 2019 (COVID-19), extensive research has emerged from across the globe to understand the pathophysiology of this novel coronavirus. Transmission of this virus is a subject of particular interest as researchers work to understand which protective and preventative measures are most effective. Despite the well understood model of aerosol-respiratory mediated transmission, the exact mechanism underlying the inoculation, infection and spread of COVID-19 is currently unknown. Given anatomical positioning and near constant exposure to aerosolized pathogens, the eye may be a possible gateway for COVID-19 infection. This critical review explores the possibility of an ocular-systemic or ocular-nasal-pulmonic pathway of COVID-19 infection and includes novel insights into the possible immunological mechanisms leading to cytokine surge.

Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection.

A proportion of patients surviving acute coronavirus disease 2019 (COVID-19) infection develop post-acute COVID syndrome (long COVID (LC)) lasting longer than 12 weeks. Here, we studied individuals with LC compared to age- and gender-matched recovered individuals without LC, unexposed donors and individuals infected with other coronaviruses. Patients with LC had highly activated innate immune cells, lacked naive T and B cells and showed elevated expression of type I IFN (IFN-ß) and type III IFN (IFN-λ1) that remained persistently high at 8 months after infection. Using a log-linear classification model, we defined an optimal set of analytes that had the strongest association with LC among the 28 analytes measured. Combinations of the inflammatory mediators IFN-ß, PTX3, IFN-γ, IFN-λ2/3 and IL-6 associated with LC with 78.5-81.6% accuracy. This work defines immunological parameters associated with LC and suggests future opportunities for prevention and treatment.

[Occupational safety and health management of COVID-19 at a company in the Peruvian fishing sector]. / Gestión de la seguridad y salud en el trabajo frente al Covid-19 en una empresa del sector pesquero peruano.

OBJECTIVE: To evaluate the occupational safety and health management of COVID-19 at a company in the Peruvian fishing sector Methods: The independent variable was occupational safety and health management, defined as the implementation of preventive and control measures in response to COVID-19. The dependent variable was defined as the number of detected COVID-19 cases and test positivity rate. We used a pre- (implementation phase) and post-test (following the implementation phase) study design. We performed a non-parametric inferential analysis to identify any significant pre- and post-test differences and any associations between the variables. RESULTS: The company initiated a strategy to detect positive cases through the use of serological tests. During the first stage, 2329 tests were conducted, yielding a positivity rate of 71%. Once prevention and control actions were implemented, the positivity rate in August 2020 had decreased to 15.65%,, a statistically significant decrease (p<0.05), as well as its relationship to the measures implemented. CONCLUSIONS: This occupational safety and health intervention significantly reduced the number of COVID-19 cases and positivity rate in this group of workers in the Peruvian fishing sector.

Objetivo: Evaluar la gestión de seguridad y salud en el trabajo de una empresa del sector pesquero peruano frente al Covid-19 Métodos: La variable independiente fue la gestión de seguridad y salud en el trabajo respecto a la implementación de acciones preventivas y de control frente al Covid-19. La variable dependiente se midió a través del número de casos detectados y la tasa de positividad de Covid-19. Se utilizó un diseño preexperimental con una preprueba, durante la implementación en proceso y una post prueba, con información recopilada al finalizar las acciones preventivas y de control. Se realizó un análisis inferencial no paramétrico para establecer diferencias significativas entre la preprueba y la post prueba y el grado de asociación entre las variables. Resultados: La empresa inició una estrategia de detección de casos positivos a través del uso de pruebas serológicas. Durante la primera etapa, se realizaron 2329 pruebas que arrojaron un 71% de positividad. Una vez que se implementaron las acciones de prevención y control la tasa de positividad se redujo a un 15.65% durante agosto del 2020. Las pruebas inferenciales mostraron un nivel de significación (p<0.05) en la reducción obtenida, así como en la relación de esta con las medidas adoptadas. Conclusiones: Una adecuada gestión de seguridad y salud en el trabajo frente al Covid-19 redujo de manera significativa el número de casos detectados y la tasa de positividad del Covid-19 en trabajadores del sector pesquero peruano.

The Effects of a Brief Lifestyle Intervention on the Health of Overweight Airline Pilots during COVID-19: A 12-Month Follow-Up Study.

The aim of this study was to perform a 12-month follow-up of health parameters after a 17-week lifestyle intervention in overweight airline pilots. A parallel-group (intervention and control) study was conducted amongst 72 overweight airline pilots (body mass index > 25) over a 12-month period following the emergence of COVID-19. The intervention group (n = 35) received a personalized dietary, sleep, and physical activity program over a 17-week period. The control group (n = 37) received no intervention. Measurements for subjective health (physical activity, sleep quality and quantity, fruit and vegetable intake, and self-rated health) via an electronic survey, and objective measures of body mass and blood pressure were taken at baseline and at 12 months. Significant interactions for group × time from baseline to 12-months were found for all outcome measures (p < 0.001). Body mass and mean arterial pressure significantly decreased in the intervention group when compared to the control group (p < 0.001). Outcome measures for subjective health (physical activity, sleep quality and quantity, fruit and vegetable intake, and self-rated health) significantly increased in the intervention group when compared to the control group (p < 0.001). Results provide preliminary evidence that a brief three-component healthy sleep, diet and physical activity intervention can elicit and sustain long-term improvements in body mass and blood pressure management, health behaviors, and perceived subjective health in pilots and may support quality of life during an unprecedented global pandemic.

Epidemics And Disability

This essay argues that considering disability and disability history needs to be part of any history of epidemics. Recent scholarship has shown the many intersections of disability history and history of medicine. This essay argues that disability plays many roles in an epidemic from establishing pre-existing conditions, to affecting the acute phase of the disease, to creating lingering disabilities in the long aftermath. Histories of epidemics that ignore the many ways in which disability affects the experience of an epidemic are incomplete.

Heat and Humidity for Bioburden Reduction of N95 Filtering Facepiece Respirators.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has caused a global shortage of single-use N95 filtering facepiece respirators (FFRs). A combination of heat and humidity is a promising method for N95 FFR decontamination in crisis-capacity conditions; however, an understanding of its effect on viral inactivation and N95 respirator function is crucial to achieving effective decontamination. Objective: We reviewed the scientific literature on heat-based methods for decontamination of N95 FFRs contaminated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and viral analogues. We identified key parameters for SARS-CoV-2 bioburden reduction while preserving N95 fit and filtration, as well as methods that are likely ineffective. Key Findings: Viral inactivation by humid heat is highly sensitive to temperature, humidity, duration of exposure, and the local microenvironment (e.g., dried saliva). A process that achieves temperatures of 70-85°C and relative humidity >50% for at least 30 min is likely to inactivate SARS-CoV-2 (>3-log reduction) on N95 respirators while maintaining fit and filtration efficiency for three to five cycles. Dry heat is significantly less effective. Microwave-generated steam is another promising approach, although less studied, whereas 121°C autoclave treatments may damage some N95 FFRs. Humid heat will not inactivate all microorganisms, so reprocessed N95 respirators should be reused only by the original user. Conclusions: Effective bioburden reduction on N95 FFRs during the COVID-19 pandemic requires inactivation of SARS-CoV-2 and preservation of N95 fit and filtration. The literature suggests that humid heat protocols can achieve effective bioburden reduction. Proper industrial hygiene, biosafety controls, and clear protocols are required to reduce the risks of N95 reprocessing and reuse.

The effectiveness of a 17-week lifestyle intervention on health behaviors among airline pilots during COVID-19.

PURPOSE: The aim of this study was to evaluate the efficacy of a 17-week, 3-component lifestyle intervention for enhancing health behaviors during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A parallel-group (intervention and control) study was conducted amongst 79 airline pilots over a 17-week period during the COVID-19 pandemic. The intervention group (n = 38) received a personalized sleep, dietary, and physical activity (PA) program. The control group (n = 41) received no intervention. Outcome measures for sleep, fruit and vegetable intake, PA, and subjective health were measured though an online survey before and after the 17-week period. The changes in outcome measures were used to determine the efficacy of the intervention. RESULTS: Significant main effects for time × group were found for International Physical Activity Questionnaire-walk (p = 0.02) and for all other outcome measures (p < 0.01). The intervention group significantly improved in sleep duration (p < 0.01; d = 1.35), Pittsburgh Sleep Quality Index score (p < 0.01; d = 1.14), moderate-to-vigorous PA (p < 0.01; d = 1.44), fruit and vegetable intake (p < 0.01; d = 2.09), Short Form 12v2 physical score (p < 0.01; d = 1.52), and Short Form 12v2 mental score (p < 0.01; d = 2.09). The control group showed significant negative change for sleep duration, Pittsburgh Sleep Quality Index score, and Short Form 12v2 mental score (p < 0.01). CONCLUSION: Results provide preliminary evidence that a 3-component healthy sleep, eating, and PA intervention elicit improvements in health behaviors and perceived subjective health in pilots and may improve quality of life during an unprecedented global pandemic.

Evolutionary perspectives on human behavior during the coronavirus pandemic: Insights from game theory.

The coronavirus pandemic constitutes a global challenge to society and medicine. Here, we review evolutionary insights that are relevant for the understanding of how people respond to the pandemic and what to expect in the aftermath of the crisis. Specifically, we argue that the behavioral immune system (BIS) and sickness behavior (SB) comprise two adaptive responses to impending and actual infection, respectively, and that individuals activating their BIS differ from those showing SB in important ways that may have implications for the prevention and treatment of COVID-19. Moreover, we reframe some of the behavioral health issues associated with the pandemic in a game-theoretical scenario, illustrating the difficulties that arise when public health is treated as a 'public good'. Lay summary: The coronavirus pandemic constitutes a global challenge to society and medicine. In this article, we employ evolutionary theory to improve our understanding of how people respond to the pandemic. Specifically, we argue that human behavior is guided by ancient mechanisms involving either the avoidance of infection or defense against attacks in times of enhanced vulnerability. Moreover, we reframe some of the behavioral health issues associated with the pandemic in a game-theoretical scenario. This helps understand why most people comply with rules of social distancing, while a minority fails to do so for very different reasons. The evolutionary perspective also allows making some predictions for the course of the pandemic.

Dynamic linkage of COVID-19 test results between Public Health England's Second Generation Surveillance System and UK Biobank.

UK Biobank (UKB) is an international health resource enabling research into the genetic and lifestyle determinants of common diseases of middle and older age. It comprises 500 000 participants. Public Health England's Second Generation Surveillance System is a centralized microbiology database covering English clinical diagnostics laboratories that provides national surveillance of legally notifiable infections, bacterial isolations and antimicrobial resistance. We previously developed secure, pseudonymized, individual-level linkage of these systems. In this study, we implemented rapid dynamic linkage, which allows us to provide a regular feed of new COVID-19 (SARS-CoV-2) test results to UKB to facilitate rapid and urgent research into the epidemiological and human genetic risk factors for severe infection in the cohort. Here, we have characterized the first 1352 cases of COVID-19 in UKB participants, of whom 895 met our working definition of severe COVID-19 as inpatients hospitalized on or after 16 March 2020. We found that the incidence of severe COVID-19 among UKB cases was 27.4 % lower than the general population in England, although this difference varied significantly by age and sex. The total number of UKB cases could be estimated as 0.6 % of the publicly announced number of cases in England. We considered how increasing case numbers will affect the power of genome-wide association studies. This new dynamic linkage system has further potential to facilitate the investigation of other infections and the prospective collection of microbiological cultures to create a microbiological biobank (bugbank) for studying the interaction of environment, human and microbial genetics on infection in the UKB cohort.