Evaluating vacant middle seats and masks as Coronavirus exposure reduction strategies in aircraft cabins using particle tracer experiments and computational fluid dynamics simulations.

Aircraft cabins have high-performance ventilation systems, yet typically hold many persons in close proximity for long durations. The current study estimated airborne virus exposure and infection reductions when middle seats are vacant compared to full occupancy and when passengers wear surgical masks in aircraft. Tracer particle data reported by U.S. Transportation Command (TRANSCOM) and CFD simulations reported by Boeing were used along with NIOSH data, to build nonlinear regression models with particle exposure and distance from particle source as variables. These models that estimate exposure at given distances from the viral source were applied to evaluate exposure reductions from vacant middle seats. Reductions averaged 54% for the seat row where an infectious passenger is located and 36% for a 24-row cabin containing one infectious passenger, with middle seats vacant. Analysis of the TRANSCOM data showed that universal masking (surgical masks) reduced exposures by 62% and showed masking and physical distancing provide further reductions when practiced together. For a notional scenario involving 10 infectious passengers, compared with no intervention, masking, distancing, and both would prevent 6.2, 3.8, and 7.6 secondary infections, respectively, using the Wells-Riley equation. These results suggest distancing alone, masking alone, and these practiced together reduce SARS CoV-2 exposure risk in increasing order of effectiveness, when an infectious passenger is present.

Discovery and Development Strategies for SARS-CoV-2 NSP3 Macrodomain Inhibitors.

The worldwide public health and socioeconomic consequences caused by the COVID-19 pandemic highlight the importance of increasing preparedness for viral disease outbreaks by providing rapid disease prevention and treatment strategies. The NSP3 macrodomain of coronaviruses including SARS-CoV-2 is among the viral protein repertoire that was identified as a potential target for the development of antiviral agents, due to its critical role in viral replication and consequent pathogenicity in the host. By combining virtual and biophysical screening efforts, we discovered several experimental small molecules and FDA-approved drugs as inhibitors of the NSP3 macrodomain. Analogue characterisation of the hit matter and crystallographic studies confirming binding modes, including that of the antibiotic compound aztreonam, to the active site of the macrodomain provide valuable structure-activity relationship information that support current approaches and open up new avenues for NSP3 macrodomain inhibitor development.

Characterisation of urban environment and activity across space and time using street images and deep learning in Accra.

The urban environment influences human health, safety and wellbeing. Cities in Africa are growing faster than other regions but have limited data to guide urban planning and policies. Our aim was to use smart sensing and analytics to characterise the spatial patterns and temporal dynamics of features of the urban environment relevant for health, liveability, safety and sustainability. We collected a novel dataset of 2.1 million time-lapsed day and night images at 145 representative locations throughout the Metropolis of Accra, Ghana. We manually labelled a subset of 1,250 images for 20 contextually relevant objects and used transfer learning with data augmentation to retrain a convolutional neural network to detect them in the remaining images. We identified 23.5 million instances of these objects including 9.66 million instances of persons (41% of all objects), followed by cars (4.19 million, 18%), umbrellas (3.00 million, 13%), and informally operated minibuses known as tro tros (2.94 million, 13%). People, large vehicles and market-related objects were most common in the commercial core and densely populated informal neighbourhoods, while refuse and animals were most observed in the peripheries. The daily variability of objects was smallest in densely populated settlements and largest in the commercial centre. Our novel data and methodology shows that smart sensing and analytics can inform planning and policy decisions for making cities more liveable, equitable, sustainable and healthy.

Lessons learned and lessons missed: impact of the coronavirus disease 2019 (COVID-19) pandemic on all-cause mortality in 40 industrialised countries and US states prior to mass vaccination.

Background: Industrialised countries had varied responses to the coronavirus disease 2019 (COVID-19) pandemic, and how they adapted to new situations and knowledge since it began. These differences in preparedness and policy may lead to different death tolls from COVID-19 as well as other diseases. Methods: We applied an ensemble of 16 Bayesian probabilistic models to vital statistics data to estimate the impacts of the pandemic on weekly all-cause mortality for 40 industrialised countries from mid-February 2020 through mid-February 2021, before a large segment of the population was vaccinated in these countries. Results: Over the entire year, an estimated 1,410,300 (95% credible interval 1,267,600-1,579,200) more people died in these countries than would have been expected had the pandemic not happened. This is equivalent to 141 (127-158) additional deaths per 100,000 people and a 15% (14-17) increase in deaths in all these countries combined. In Iceland, Australia and New Zealand, mortality was lower than would be expected if the pandemic had not occurred, while South Korea and Norway experienced no detectable change in mortality. In contrast, the USA, Czechia, Slovakia and Poland experienced at least 20% higher mortality. There was substantial heterogeneity across countries in the dynamics of excess mortality. The first wave of the pandemic, from mid-February to the end of May 2020, accounted for over half of excess deaths in Scotland, Spain, England and Wales, Canada, Sweden, Belgium, the Netherlands and Cyprus. At the other extreme, the period between mid-September 2020 and mid-February 2021 accounted for over 90% of excess deaths in Bulgaria, Croatia, Czechia, Hungary, Latvia, Montenegro, Poland, Slovakia and Slovenia. Conclusions: Until the great majority of national and global populations have vaccine-acquired immunity, minimising the death toll of the pandemic from COVID-19 and other diseases will require actions to delay and contain infections and continue routine health care.

Lessons learned and lessons missed: impact of the coronavirus disease 2019 (COVID-19) pandemic on all-cause mortality in 40 industrialised countries prior to mass vaccination

Background: Industrialised countries had varied responses to the coronavirus disease 2019 (COVID-19) pandemic, and how they adapted to new situations and knowledge since it began. These differences in preparedness and policy may lead to different death tolls from COVID-19 as well as other diseases. Methods: We applied an ensemble of 16 Bayesian probabilistic models to vital statistics data to estimate the impacts of the pandemic on weekly all-cause mortality for 40 industrialised countries from mid-February 2020 through mid-February 2021, before a large segment of the population was vaccinated in these countries. Results: Over the entire year, an estimated 1,410,300 (95% credible interval 1,267,600-1,579,200) more people died in these countries than would have been expected had the pandemic not happened. This is equivalent to 141 (127-158) additional deaths per 100,000 people and a 15% (14-17) increase in deaths in all these countries combined. In Iceland, Australia and New Zealand, mortality was lower than would be expected if the pandemic had not occurred, while South Korea and Norway experienced no detectable change in mortality. In contrast, the USA, Czechia, Slovakia and Poland experienced at least 20% higher mortality. There was substantial heterogeneity across countries in the dynamics of excess mortality. The first wave of the pandemic, from mid-February to the end of May 2020, accounted for over half of excess deaths in Scotland, Spain, England and Wales, Canada, Sweden, Belgium, the Netherlands and Cyprus. At the other extreme, the period between mid-September 2020 and mid-February 2021 accounted for over 90% of excess deaths in Bulgaria, Croatia, Czechia, Hungary, Latvia, Montenegro, Poland, Slovakia and Slovenia. Conclusions: Until the great majority of national and global populations have vaccine-acquired immunity, minimising the death toll of the pandemic from COVID-19 and other diseases will require actions to delay and contain infections and continue routine health care.

Lessons learned and lessons missed: impact of the coronavirus disease 2019 (COVID-19) pandemic on all-cause mortality in 40 industrialised countries and US states prior to mass vaccination [version 2;peer review: 2 approved]

Background: Industrialised countries had varied responses to the COVID-19 pandemic, which may lead to different death tolls from COVID-19 and other diseases. Methods: We applied an ensemble of 16 Bayesian probabilistic models to vital statistics data to estimate the number of weekly deaths if the pandemic had not occurred for 40 industrialised countries and US states from mid-February 2020 through mid-February 2021. We subtracted these estimates from the actual number of deaths to calculate the impacts of the pandemic on all-cause mortality. Results: Over this year, there were 1,410,300 (95% credible interval 1,267,600-1,579,200) excess deaths in these countries, equivalent to a 15% (14-17) increase, and 141 (127-158) additional deaths per 100,000 people. In Iceland, Australia and New Zealand, mortality was lower than would be expected in the absence of the pandemic, while South Korea and Norway experienced no detectable change. The USA, Czechia, Slovakia and Poland experienced >20% higher mortality. Within the USA, Hawaii experienced no detectable change in mortality and Maine a 5% increase, contrasting with New Jersey, Arizona, Mississippi, Texas, California, Louisiana and New York which experienced >25% higher mortality. Mid-February to the end of May 2020 accounted for over half of excess deaths in Scotland, Spain, England and Wales, Canada, Sweden, Belgium, the Netherlands and Cyprus, whereas mid-September 2020 to mid-February 2021 accounted for >90% of excess deaths in Bulgaria, Croatia, Czechia, Hungary, Latvia, Montenegro, Poland, Slovakia and Slovenia. In USA, excess deaths in the northeast were driven mainly by the first wave, in southern and southwestern states by the summer wave, and in the northern plains by the post-September period. Conclusions: Prior to widespread vaccine-acquired immunity, minimising the overall death toll of the pandemic requires policies and non-pharmaceutical interventions that delay and reduce infections, effective treatments for infected patients, and mechanisms to continue routine health care.

Life expectancy and risk of death in 6791 communities in England from 2002 to 2019: high-resolution spatiotemporal analysis of civil registration data.

BACKGROUND: High-resolution data for how mortality and longevity have changed in England, UK are scarce. We aimed to estimate trends from 2002 to 2019 in life expectancy and probabilities of death at different ages for all 6791 middle-layer super output areas (MSOAs) in England. METHODS: We performed a high-resolution spatiotemporal analysis of civil registration data from the UK Small Area Health Statistics Unit research database using de-identified data for all deaths in England from 2002 to 2019, with information on age, sex, and MSOA of residence, and population counts by age, sex, and MSOA. We used a Bayesian hierarchical model to obtain estimates of age-specific death rates by sharing information across age groups, MSOAs, and years. We used life table methods to calculate life expectancy at birth and probabilities of death in different ages by sex and MSOA. FINDINGS: In 2002-06 and 2006-10, all but a few (0-1%) MSOAs had a life expectancy increase for female and male sexes. In 2010-14, female life expectancy decreased in 351 (5·2%) of 6791 MSOAs. By 2014-19, the number of MSOAs with declining life expectancy was 1270 (18·7%) for women and 784 (11·5%) for men. The life expectancy increase from 2002 to 2019 was smaller in MSOAs where life expectancy had been lower in 2002 (mostly northern urban MSOAs), and larger in MSOAs where life expectancy had been higher in 2002 (mostly MSOAs in and around London). As a result of these trends, the gap between the first and 99th percentiles of MSOA life expectancy for women increased from 10·7 years (95% credible interval 10·4-10·9) in 2002 to reach 14·2 years (13·9-14·5) in 2019, and for men increased from 11·5 years (11·3-11·7) in 2002 to 13·6 years (13·4-13·9) in 2019. INTERPRETATION: In the decade before the COVID-19 pandemic, life expectancy declined in increasing numbers of communities in England. To ensure that this trend does not continue or worsen, there is a need for pro-equity economic and social policies, and greater investment in public health and health care throughout the entire country. FUNDING: Wellcome Trust, Imperial College London, Medical Research Council, Health Data Research UK, and National Institutes of Health Research.

Community factors and excess mortality in first wave of the COVID-19 pandemic in England.

Risk factors for increased risk of death from COVID-19 have been identified, but less is known on characteristics that make communities resilient or vulnerable to the mortality impacts of the pandemic. We applied a two-stage Bayesian spatial model to quantify inequalities in excess mortality in people aged 40 years and older at the community level during the first wave of the pandemic in England, March-May 2020 compared with 2015-2019. Here we show that communities with an increased risk of excess mortality had a high density of care homes, and/or high proportion of residents on income support, living in overcrowded homes and/or with a non-white ethnicity. We found no association between population density or air pollution and excess mortality. Effective and timely public health and healthcare measures that target the communities at greatest risk are urgently needed to avoid further widening of inequalities in mortality patterns as the pandemic progresses.

Fragment binding to the Nsp3 macrodomain of SARS-CoV-2 identified through crystallographic screening and computational docking.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) macrodomain within the nonstructural protein 3 counteracts host-mediated antiviral adenosine diphosphate-ribosylation signaling. This enzyme is a promising antiviral target because catalytic mutations render viruses nonpathogenic. Here, we report a massive crystallographic screening and computational docking effort, identifying new chemical matter primarily targeting the active site of the macrodomain. Crystallographic screening of 2533 diverse fragments resulted in 214 unique macrodomain-binders. An additional 60 molecules were selected from docking more than 20 million fragments, of which 20 were crystallographically confirmed. X-ray data collection to ultra-high resolution and at physiological temperature enabled assessment of the conformational heterogeneity around the active site. Several fragment hits were confirmed by solution binding using three biophysical techniques (differential scanning fluorimetry, homogeneous time-resolved fluorescence, and isothermal titration calorimetry). The 234 fragment structures explore a wide range of chemotypes and provide starting points for development of potent SARS-CoV-2 macrodomain inhibitors.

Long-term exposure to air-pollution and COVID-19 mortality in England: A hierarchical spatial analysis.

Recent studies suggested a link between long-term exposure to air-pollution and COVID-19 mortality. However, due to their ecological design based on large spatial units, they neglect the strong localised air-pollution patterns, and potentially lead to inadequate confounding adjustment. We investigated the effect of long-term exposure to NO2 and PM2.5 on COVID-19 mortality in England using high geographical resolution. In this nationwide cross-sectional study in England, we included 38,573 COVID-19 deaths up to June 30, 2020 at the Lower Layer Super Output Area level (n = 32,844 small areas). We retrieved averaged NO2 and PM2.5 concentration during 2014-2018 from the Pollution Climate Mapping. We used Bayesian hierarchical models to quantify the effect of air-pollution while adjusting for a series of confounding and spatial autocorrelation. We find a 0.5% (95% credible interval: -0.2%, 1.2%) and 1.4% (95% CrI: -2.1%, 5.1%) increase in COVID-19 mortality risk for every 1 µg/m3 increase in NO2 and PM2.5 respectively, after adjusting for confounding and spatial autocorrelation. This corresponds to a posterior probability of a positive effect equal to 0.93 and 0.78 respectively. The spatial relative risk at LSOA level revealed strong patterns, similar for the different pollutants. This potentially captures the spread of the disease during the first wave of the epidemic. Our study provides some evidence of an effect of long-term NO2 exposure on COVID-19 mortality, while the effect of PM2.5 remains more uncertain.

Magnitude, demographics and dynamics of the effect of the first wave of the COVID-19 pandemic on all-cause mortality in 21 industrialized countries.

The Coronavirus Disease 2019 (COVID-19) pandemic has changed many social, economic, environmental and healthcare determinants of health. We applied an ensemble of 16 Bayesian models to vital statistics data to estimate the all-cause mortality effect of the pandemic for 21 industrialized countries. From mid-February through May 2020, 206,000 (95% credible interval, 178,100-231,000) more people died in these countries than would have had the pandemic not occurred. The number of excess deaths, excess deaths per 100,000 people and relative increase in deaths were similar between men and women in most countries. England and Wales and Spain experienced the largest effect: ~100 excess deaths per 100,000 people, equivalent to a 37% (30-44%) relative increase in England and Wales and 38% (31-45%) in Spain. Bulgaria, New Zealand, Slovakia, Australia, Czechia, Hungary, Poland, Norway, Denmark and Finland experienced mortality changes that ranged from possible small declines to increases of 5% or less in either sex. The heterogeneous mortality effects of the COVID-19 pandemic reflect differences in how well countries have managed the pandemic and the resilience and preparedness of the health and social care system.