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At least 235 records · Page 13

Challenges in Automated Detection of COVID-19 Misinformation

The COVID-19 pandemic has made the dangers of the spread of misinformation obvious but despite much global effort to curbing its spread, fake information about the pandemic keeps proliferating. In this paper, we address the development of automated methods for verification of claims about COVID-19 and discuss the challenges associated with this task. We focus on labeled data collection, limitations of existing models, and difficulties of applying misinformation detection models in practical applications. Our initial analysis indicates label imbalance may be a particular challenge for developing claim verification models and we discuss options for alleviating this issue.

Herrmannova, Dasha↗

IMPECCABLE: Integrated Modeling Pipeline for COVID Cure by Assessing Better Leads

ABSTRACT The drug discovery process currently employed in the pharmaceutical industry typically requires about 10 years and $2-3 billion to deliver one new drug. This is both too expensive and too slow, especially in emergencies like the COVID-19 pandemic. In silico methodologies need to be improved both to select better lead compounds, so as to improve the efficiency of later stages in the drug discovery protocol, and to identify those lead compounds more quickly. No known methodological approach can deliver this combination of higher quality and speed. Here, we describe an Integrated Modeling PipEline for COVID Cure by Assessing Better LEads (IMPECCABLE) that employs multiple methodological innovations to overcome this fundamental limitation. We also describe the computational framework that we have developed to support these innovations at scale, and characterize the performance of this framework in terms of throughput, peak performance, and scientific results. We show that individual workflow components deliver 100× to 1000× improvement over traditional methods, and that the integration of methods, supported by scalable infrastructure, speeds up drug discovery by orders of magnitudes. IMPECCABLE has screened ~10 11 ligands and has been used to discover a promising drug candidate. These capabilities have been used by the US DOE National Virtual Biotechnology Laboratory and the EU Centre of Excellence in Computational Biomedicine.

97 MATHEMATICS AND COMPUTING↗

ComStock/COVID-19: U.S. Commercial Building Stock Analysis of COVID-19 Mitigation Strategies

ComStock is a DOE platform, with NREL as the lead developer, that models the U.S. commercial building stock using OpenStudio/EnergyPlus to perform physics-based building energy modeling simulations. The ASHRAE Epidemic Taskforce (ASHRAE-ETF) has released several COVID-19 mitigation strategies for commercial buildings. ComStock was used to analyze the impact of four strategies on the existing commercial building stock. These strategies are upgrading to MERV-13 filters, disabling demand control ventilation (DCV), increasing minimum outdoor air to 100%, and HVAC flushing mode operation. Results show the impact of each measure on energy consumption, electric consumption, gas consumption and peak electric.

30 DIRECT ENERGY CONVERSION↗

Evolution of the SARS-CoV -2 proteome in three dimensions (3D) during the first 6 months of the COVID -19 pandemic

Understanding the molecular evolution of the SARS-CoV-2 virus as it continues to spread in communities around the globe is important for mitigation and future pandemic preparedness. Three-dimensional structures of SARS-CoV-2 proteins and those of other coronavirusess archived in the Protein Data Bank were used to analyze viral proteome evolution during the first 6 months of the COVID-19 pandemic. Analyses of spatial locations, chemical properties, and structural and energetic impacts of the observed amino acid changes in >48 000 viral isolates revealed how each one of 29 viral proteins have undergone amino acid changes. Catalytic residues in active sites and binding residues in protein–protein interfaces showed modest, but significant, numbers of substitutions, highlighting the mutational robustness of the viral proteome. Energetics calculations showed that the impact of substitutions on the thermodynamic stability of the proteome follows a universal bi-Gaussian distribution. Here detailed results are presented for potential drug discovery targets and the four structural proteins that comprise the virion, highlighting substitutions with the potential to impact protein structure, enzyme activity, and protein–protein and protein–nucleic acid interfaces. Characterizing the evolution of the virus in three dimensions provides testable insights into viral protein function and should aid in structure-based drug discovery efforts as well as the prospective identification of amino acid substitutions with potential for drug resistance.

59 BASIC BIOLOGICAL SCIENCES↗

A Multi-Region SEIR Model Incorporating Inter-County Mobility and Time-Dependent Transmission Dynamics: Application to COVID-19 Disease Outbreak Data in North Carolina.

Classical infectious disease compartmental models typically do not incorporate spatial heterogeneity or mobility. We develop a multi-region susceptible-exposed-infected-recovered (SEIR) model in which disease dynamics are coupled via inter-region mobility and the transmission rate is both region and time dependent. We calibrate the model using rolling averages of daily COVID-19 data in all 100 North Carolina counties. Mobility parameters are prescribed using daily inter-county commuter data. The number of transmission rate parameters is substantially reduced by hypothesizing that the dynamics correlate with county-level population density. Parameter estimation is carried out using several objective functions with error terms at different scales. An additive combination of least squares error at the county-level and the state-level, along with a quadratic transmission rate polynomial, yields the lowest overall error at both spatial scales. The calibrated model is used to simulate regional effects of perturbing disease transmission rates in adjacent counties and to illustrate effects of the state’s mobility infrastructure on disease dynamics and spread for a new disease outbreak.

COVID-19 modeling↗

Black Swan Event Small-Sample Transfer Learning (BEST-L) and its Case Study on Electrical Power Prediction in COVID-19

The black swan event will usually cause a great impact on the normal operation of society. The scarcity of such events leads to a lack of relevant data and challenges in dealing with related problems. Different situations also make the traditional methods invalid. In this paper, a transfer learning framework and a convolutional neuron network are proposed to deal with the black swan small-sample events (BEST-L). Taking the COVID-19 as a typical black swan event, the BEST-L is utilized to achieve accurate mid-term load forecasting using the relationship between economy and electricity consumption. The experiment results show that the transfer learning model can effectively learn the basic knowledge about the relationship between the adopted input and output data and use a relatively small amount of data during the black swan event to improve the target areas' generalization. The approach and results can provide an effective approach to respond and react to sudden changes quickly and effectively in similar open problems.

black swan event↗

COVID-19 impacts on residential occupancy schedules and activities in U.S. Homes in 2020 using ATUS

Many aspects of the daily lives of those living in the United States were substantially impacted by the COVID-19 pandemic in the year 2020. A broad diversity of measures was implemented to curb the spread of the virus, many of which included adjustments to where and how people worked, went to school, and otherwise conducted their daily lives compared to pre-pandemic times. This has impacted how residential buildings are used, how much time people spend in their homes, and as a result, how much energy these buildings consume. The main objective of this study is to analyze, at a national scale, the differences in the occupancy schedules and activities conducted in homes in the U.S., as compared to pre-pandemic. 15 years of American Time Use Survey and Current Population Survey data, from 2006 to 2020, was used in this study to analyze the occupancy schedules for both pandemic (2020) and pre-pandemic (2006–2019) times. These impacts were also analyzed with respect to variables including, weekday/weekend, month of the year, age of the occupants, household income, and household size. The impact of the pandemic on occupant schedules were most substantial in the initial months, whereas as the months progressed, these occupancy profiles slowly changed. Across 2020, people spent, on average, 8 % more time (1.9 h) in their home on weekdays, and 3–6 % (1.2 h) on weekend days. The percentage of time spent for different activities and locations within homes were also studied. For 1-member households, their time spent at home decreased whereas for 2-, 3-, and 4- member households, they spent more time at home. Overall, people spent around 45% more time doing office- and work-related activities at home compared to pre-pandemic, which is likely due to increased remote working and schooling. This research helps to improve the understanding of the occupancy presence and absence profiles in U.S. residential buildings due to the pandemic and provides new insights as to modified profiles for researchers, building designers, and policy makers.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

Persistent high PM 2.5 pollution driven by unfavorable meteorological conditions during the COVID-19 lockdown period in the Beijing-Tianjin-Hebei region, China

Lockdown measures to curtail the COVID-19 pandemic in China halted most nonessential activities on January 23, 2020. Despite significant reductions in anthropogenic emissions, the Beijing-Tianjin-Hebei (BTH) region still experienced high air pollution concentrations. In this work, employing two emissions reduction scenarios, the Community Multiscale Air Quality (CMAQ) model was used to investigate the PM 2.5 concentrations change in this region. The model using the scenario (C3) with greater traffic reductions performed better compared to the observed PM 2.5 . Compared with the no reductions base-case (scenario C1), PM 2.5 reductions with scenario C3 were 2.70, 2.53, 2.90, 2.98, 3.30, 2.81, 2.82, 2.98, 2.68, and 2.83 µg/m 3 in Beijing, Tianjin, Shijiazhuang, Baoding, Cangzhou, Chengde, Handan, Hengshui, Tangshan, and Xingtai, respectively. During high-pollution days in scenario C3, the percentage reductions in PM 2.5 concentrations in Beijing, Tianjin, Shijiazhuang, Baoding, Cangzhou, Chengde, Handan, Hengshui, Tangshan, and Xingtai were 3.76, 3.54, 3.28, 3.22, 3.57, 3.56, 3.47, 6.10, 3.61, and 3.67%, respectively. However, significant increases caused by unfavorable meteorological conditions counteracted the emissions reduction effects resulting in high air pollution in BTH region during the lockdown period. This study shows that effective air pollution control strategies incorporating these results are urgently required in BTH to avoid severe pollution.

54 ENVIRONMENTAL SCIENCES↗

COVID 19 vaccine distribution solution to the last mile challenge: Experimental and simulation studies of ultra-low temperature refrigeration system

Most COVID-19 vaccines require ambient temperature control for transportation and storage. Both Pfizer and Moderna vaccines are based on mRNA and lipid nanoparticles requiring low temperature storage. The Pfizer vaccine requires ultra-low temperature storage (between -80 °C and -60 °C), while the Moderna vaccine requires -30 °C storage. Pfizer has designed a reusable package for transportation and storage that can keep the vaccine at the target temperature for 10 days. However, the last stage of distribution is quite challenging, especially for rural or suburban areas, where local towns, pharmacy chains and hospitals may not have the infrastructure required to store the vaccine. Also, the need for a large amount of ultra-low temperature refrigeration equipment in a short time period creates tremendous pressure on the equipment suppliers. In addition, there is limited data available to address ancillary challenges of the distribution framework for both transportation and storage stages. As such, there is a need for a quick, effective, secure, and safe solution to mitigate the challenges faced by vaccine distribution logistics. The study proposes an effective, secure, and safe ultra-low temperature refrigeration solution to resolve the vaccine distribution last mile challenge. Furthermore, the approach is to utilize commercially available products, such as refrigeration container units, and retrofit them to meet the vaccine storage temperature requirement. Both experimental and simulation studies are conducted to evaluate the technical merits of this solution with the ability to control temperature at -30 °C or -70 °C as part of the last mile supply chain for vaccine candidates.

60 APPLIED LIFE SCIENCES↗

Synthetic proteins for COVID-19 diagnostics

There is an urgent need for inexpensive, rapid and specific antigen-based assays to test for vaccine efficacy and detect infection with SARS-CoV-2 and its variants. We have identified a small, synthetic protein (JS7), representing a region of maximum variability within the receptor binding domain (RBD), which binds antibodies in sera from nine patients with PCR-verified COVID-19 of varying severity. Antibodies binding to either JS7 or the SARS-CoV-2 recombinant RBD, as well as those that disrupt binding between a fragment of the ACE2 receptor and the RBD, are proportional to disease severity and clinical outcome. Binding to JS7 was inhibited by linear peptides from the RBD interface with ACE2. Variants of JS7, such as E484K or N501Y, can be quickly synthesized in pure form in large quantities by automated methods. JS7 and related synthetic antigens can provide a basis for specific diagnostics for SARS-CoV-2 infections.

59 BASIC BIOLOGICAL SCIENCES↗

Extended use of face masks during the COVID-19 pandemic - Thermal conditioning and spray-on surface disinfection

The current COVID-19 pandemic has resulted in globally constrained supplies for face masks and personal protective equipment (PPE). Production capacity is limited in many countries and the future course of the pandemic will likely continue with shortages for high quality masks and PPE in the foreseeable future. Therefore, expectations are that mask reuse, extended wear and similar approaches will enhance the availability of personal protective measures. Repeated thermal disinfection could be an important option and likely easier implemented in some situations, at least on the small scale, than UV illumination, irradiation or hydrogen peroxide vapor exposure. In this paper, an overview on thermal responses and ongoing filtration performance of multiple face mask types is provided. Most masks have adequate material properties to survive a few cycles (i.e. 30 min disinfection steps) of thermal exposure in the 75°C regime. Some are more easily affected, as seen by the fusing of plastic liner or warping, given that preferred conditioning temperatures are near the softening point for some of the plastics and fibers used in these masks. Hence adequate temperature control is equally important. As guidance, disinfectants sprayed via dilute solutions maintain a surface presence over extended time at 25 and 37°C. Some spray-on alcohol-based solutions containing disinfectants were gently applied to the top surface of masks. Neither moderate thermal aging (less than 24 h at 80 and 95°C) nor gentle application of surface disinfectant sprays resulted in measurable loss of mask filter performance. Subject to bio-medical concurrence (additional checks for virus kill efficiency) and the use of low risk non-toxic disinfectants, such strategies, either individually or combined, by offering additional anti-viral properties or short term refreshing, may complement reuse options of professional masks or the now ubiquitous custom-made face masks with their often unknown filtration effectiveness.

36 MATERIALS SCIENCE↗

The concentration of BTEX in selected urban areas of Malaysia during the COVID-19 pandemic lockdown

Volatile organic compounds (VOCs) such as benzene, toluene, ethylbenzene and xylene (BTEX) are air pollutants that harm human health. This study aims to identify BTEX concentrations before the lockdown known as the Movement Control Order was imposed (BMCO), during the implementation of the Movement Control Order (MCO), and then during the Conditional Movement Control Order (CMCO). These orders were introduced during the COVID-19 pandemic in Malaysia. The study utilised data measured by the continuous monitoring of BTEX using online gas chromatography instruments located at three urban area stations. Here, the results showed that the BTEX concentrations reduced by between –38% and –46% during the MCO compared to the BMCO period. The reduction of human mobility during the MCO and CMCO influenced the lower BTEX concentrations recorded at a station within the Kuala Lumpur area. The results of the BTEX diagnostic ratios and principal component analysis showed that the major source of BTEX, especially during the BMCO and CMCO periods, was motor vehicle emissions. Further investigation, using correlation analysis and polar plots, showed that the BTEX concentrations were also influenced by meteorological variables such as wind speed, air temperature and relative humidity.

54 ENVIRONMENTAL SCIENCES↗

Screening of Therapeutic Agents for COVID-19 Using Machine Learning and Ensemble Docking Studies

The current pandemic demands a search for therapeutic agents against the novel coronavirus SARS-CoV-2. In this work, we present an efficient computational strategy that combines machine learning (ML)-based models and high-fidelity ensemble docking studies to enable rapid screening of possible therapeutic ligands. Targeting the binding affinity of molecules for either the isolated SARS-CoV-2 S-protein at its host receptor region or the S-protein:human ACE2 interface complex, we screen ligands from drug and biomolecule data sets that can potentially limit and/or disrupt the host-virus interactions. Top scoring one hundred eighty-seven ligands (with 75 approved by the Food and Drug Administration) are further validated by all atom docking studies. Important molecular descriptors ( 2 χ n , topological surface area, and ring count) and promising chemical fragments (oxolane, hydroxy, and imidazole) are identified to guide future experiments. Overall, this work expands our knowledge of small-molecule treatment against COVID-19 and provides a general screening pathway (combining quick ML models with expensive high-fidelity simulations) for targeting several chemical/biochemical problems.

60 APPLIED LIFE SCIENCES↗

Disentangling the Impact of the COVID‐19 Lockdowns on Urban NO 2 From Natural Variability

Abstract TROPOMI satellite data show substantial drops in nitrogen dioxide (NO 2 ) during COVID‐19 physical distancing. To attribute NO 2 changes to NO x emissions changes over short timescales, one must account for meteorology. We find that meteorological patterns were especially favorable for low NO 2 in much of the United States in spring 2020, complicating comparisons with spring 2019. Meteorological variations between years can cause column NO 2 differences of ~15% over monthly timescales. After accounting for solar angle and meteorological considerations, we calculate that NO 2 drops ranged between 9.2% and 43.4% among 20 cities in North America, with a median of 21.6%. Of the studied cities, largest NO 2 drops (>30%) were in San Jose, Los Angeles, and Toronto, and smallest drops (<12%) were in Miami, Minneapolis, and Dallas. These normalized NO 2 changes can be used to highlight locations with greater activity changes and better understand the sources contributing to adverse air quality in each city.

54 ENVIRONMENTAL SCIENCES↗

Time-dependent heterogeneity leads to transient suppression of the COVID-19 epidemic, not herd immunity

Significance Epidemics generally spread through a succession of waves that reflect factors on multiple timescales. Here, we develop a general approach bridging across these timescales and demonstrate how to incorporate population heterogeneity into a wide class of epidemiological models. We demonstrate that a fragile state of transient collective immunity emerges during early, high-paced stages of the epidemic, leading to suppression of individual epidemic waves. However, this state is not an indication of lasting herd immunity: Subsequent waves may emerge due to stochastic changes in individual social activity. Parameters of transient collective immunity are estimated using empirical data from the COVID-19 epidemic in several US locations.

59 BASIC BIOLOGICAL SCIENCES↗

COVID-19 pandemic reveals persistent disparities in nitrogen dioxide pollution

We leverage the unparalleled changes in human activity during COVID-19 and the unmatched capabilities of the TROPOspheric Monitoring Instrument to understand how lockdowns impact ambient nitrogen dioxide (NO 2 ) pollution disparities in the United States. The least White communities experienced the largest NO 2 reductions during lockdowns; however, disparities between the least and most White communities are so large that the least White communities still faced higher NO 2 levels during lockdowns than the most White communities experienced prior to lockdowns, despite a ~50% reduction in passenger vehicle traffic. Similar findings hold for ethnic, income, and educational attainment population subgroups. Future strategies to reduce NO 2 disparities will need to target emissions from heavy-duty vehicles.

TROPOMI↗

Oxidative stress is a shared characteristic of ME/CFS and Long COVID

Over 65 million individuals worldwide are estimated to have Long COVID (LC), a complex multisystemic condition marked by fatigue, post-exertional malaise, and other symptoms resembling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). With no clinically approved treatments or reliable diagnostic markers, there is an urgent need to define the molecular underpinnings of these conditions. By studying bioenergetic characteristics of peripheral blood lymphocytes in 25 healthy controls, 27 ME/CFS, and 20 LC donors, we find both ME/CFS and LC donors exhibit signs of elevated oxidative stress, especially in the memory subset. Using a combination of flow cytometry, RNA-seq, mass spectrometry, and systems chemistry analysis, we observed aberrations in reactive oxygen species (ROS) clearance pathways including elevated glutathione levels, decreases in mitochondrial superoxide dismutase protein levels, and glutathione peroxidase 4–mediated lipid oxidative damage. Strikingly, these redox pathways changes show sex-specific trends. While ME/CFS females exhibit higher total ROS and mitochondrial calcium levels, males have normal ROS levels, with pronounced mitochondrial lipid oxidative damage. In females, these higher ROS levels correlate with T cell hyperproliferation, consistent with the known role of elevated ROS in initiating proliferation. This hyperproliferation can be attenuated by metformin, suggesting this Food and Drug Administration (FDA)-approved drug as a possible treatment, as also suggested by a recent clinical study of LC patients. Moreover, these results suggest a shared mechanistic basis for the systemic phenotypes of ME/CFS and LC, which can be detected by quantitative blood cell measurements, and that effective, patient-tailored drugs might be discovered using standard lymphocyte stimulation assays.

ME/CFS↗