title: The effect of Arbidol Hydrochloride on reducing mortality of Covid-19 patients: a retrospective study of real world date from three hospitals in Wuhan

text: BACKGROUND The worldwide COVID-19 pandemic develops rapidly. There is a pressing need to find an effective therapy. METHODS We have assembled a cohort consisting 504 hospitalized COVID-19. Information of patients characteristics and antiviral medication use during hospital stay is collected. The study objective is to evaluate the treatment efficacy of selected antiviral medications on mortality and lesion absorption based on chest CT scan. RESULTS The overall mortality rate was 15.67% in the cohort. Older age, lower SpO2 level, bigger lesion, early admission data, and the presence of pre-existing conditions were associated with higher mortality. After adjusting for sex, pre-existing condition, age, SpO2, lesion size, admission data, hospital, and anti-viral medications use, Arbidol and Oseltamivir use is associated with a reduction in mortality. The OR is 0.183 (95% CI, 0.075 to 0.446; p<0.001) for Arbidol and 0.220 (95% CI, 0.069 to 0.707; p=0.011) for Oseltamivir. Compared with patients taking neither Arbidol nor Oseltamivir, the OR is 0.253 (95% CI, 0.064 to 1.001; p=0.050) for patients taking Oseltamivir only; 0.190 (95% CI, 0.076 to 0.473; p<0.001) for patients taking Arbidol only; and 0.030 (95% CI, 0.003 to 0.310; p=0.003) for patients taking both, after adjusting for patients characteristics and Lopinavir/Ritonavir use. Similarly, Arbidol is also associated with faster lesion absorption after adjusting for patients characteristics as well as Oseltamivir and Lopinavir/Ritonavir use. CONCLUSIONS Arbidol is able to substantially associated with a reduction in mortality among hospitalized COVID-19 patients. The combination of Arbidol and Oselmativir may further associated with a reduction in mortality. There is no proven treatment benefit of Lopinavir/Ritonavir.


title: Detection of SARS-CoV-2 RNA by direct RT-qPCR on nasopharyngeal specimens without extraction of viral RNA

text: To circumvent the limited availability of RNA extraction reagents, we developed a protocol for direct RT-qPCR to detect SARS-CoV-2 in nasopharyngeal swabs. Incubation of specimens at 65oC for 10 minutes along with the use of TaqPath 1-Step RT-qPCR Master Mix provides higher analytical sensitivity for detection of SARS-CoV-2 RNA than many other commercial and laboratory-developed methods. In 132 specimens submitted for SARS-CoV-2 testing, the sensitivity, specificity and accuracy of our optimized approach were 95%, 99% and 98.5%, respectively, with reference to results obtained by a standard approach involving RNA extraction. Also, the RT-qPCR CT values obtained by the two methods were highly correlated.


title: Is the turtle still plodding along? Public management reform in Germany

text: Public management reforms in Germany have long been characterized by slow-moving incrementalism and maintenance of its administrative system’s central characteristics. This article reviews recent developments in administrative reforms against the background of the traditional German reform style. More ambitious reform efforts in the field of digitalization raise conceptual puzzles related to the conditions under which incrementalism can generate substantive change–and at what point incremental reforms give way to more rapid patterns of change. The article also discusses the implications of the ongoing COVID-19 crisis on public management reforms.


title: Shared SARS-CoV-2 diversity suggests localised transmission of minority variants

text: We gratefully acknowledge the UK COVID-19 Genomics Consortium (COG UK) for funding, and Public Health Wales / Cardiff University and MRC-University of Glasgow Centre for Virus Research for making their COG-UK sequence data publicly available. COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) and Genome Research Limited, operating as the Wellcome Sanger Institute. The research was supported by the Wellcome Trust Core Award Grant Number 203141/Z/16/Z with funding from the NIHR Oxford BRC. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. We are deeply grateful to Robert Esnouf and the BMRC Research Computing team for unfailing assistance with computational infrastructure. We also thank Benjamin Carpenter and James Docker for assistance in the laboratory, and Lorne Lonie, Maria Lopopolo, Chris Allen, John Broxholme and the WHG high-throughput genomics team for sequencing and quality control. The HIV clone p92BR025.8 was obtained through the Centre For AIDS Reagents from Drs Beatrice Hahn and Feng Gao, and the UNAIDS Virus Network (courtesy of the NIH AIDS Research and Reference Reagent Program). KAL is supported by The Wellcome Trust and The Royal Society (107652/Z/15/Z). MH, LF, MdC, GMC, NO, LAD, DB, CF and TG are supported by Li Ka Shing Foundation funding awarded to CF. PS is supported by a Wellcome Investigator Award (WT103767MA). Summary SARS-CoV-2, the causative agent of COVID-19, emerged in late 2019 causing a global pandemic, with the United Kingdom (UK) one of the hardest hit countries. Rapid sequencing and publication of consensus genomes have enabled phylogenetic analysis of the virus, demonstrating SARS-CoV-2 evolves relatively slowly1, but with multiple sites in the genome that appear inconsistent with the overall consensus phylogeny2. To understand these discrepancies, we used veSEQ3, a targeted RNA-seq approach, to quantify minor allele frequencies in 413 clinical samples from two UK locations. We show that SARS-CoV-2 infections are characterised by extensive within-host diversity, which is frequently shared among infected individuals with patterns consistent with geographical structure. These results were reproducible in data from two other sequencing locations in the UK, where we find evidence of mixed infection by major circulating lineages with patterns that cannot readily be explained by artefacts in the data. We conclude that SARS-CoV-2 diversity is transmissible, and propose that geographic patterns are generated by transient co-circulation of distinct viral populations. Co-transmission of mixed populations could open opportunities for resolving clusters of transmission and understanding pathogenesis.


title: Paying the Price for a Broken Healthcare System: Rethinking Employment, Labor, and Work in a Post-Pandemic World

text: Even before the word pandemic reentered the lexicon, pressures stemming from institutional and technological change challenged policymakers and provider organizations to rethink core features of the manner in which we deliver healthcare. This essay introduces a special issue devoted to the consequences of change on the healthcare sector’s varied stakeholders. It does so in the context of our eventual, post-coronavirus reemergence and a renewed interest in remaking the healthcare system in light of its obvious deficiencies. Towards that end, we introduce the five papers composing this special issue, each of which informs the ways that change actually transpires in healthcare organizations and systems.


title: Public perspectives on social distancing and other protective measures in Europe: a cross-sectional survey study during the COVID-19 pandemic

text: Objectives: The extent to which people implement government-issued protective measures is critical in preventing further spread of coronavirus disease 2019 (COVID-19) caused by coronavirus SARS-CoV-2. Our study aimed to evaluate the public belief in the effectiveness of protective measures, the reported implementation of these measures in daily life, and to identify communication channels used to acquire relevant information on COVID-19 in European countries. Design: A cross-sectional online survey available in multiple languages was disseminated on social media starting March 19th, 2020. After five days, we computed descriptive statistics for countries with more than 500 respondents. Each day, we compiled and categorized community containment measures enacted in each country by stringency (stage I-IV). Response collection continued for one week to explore possible dynamics as containment strategies intensified. Participants: In total, 9,796 adults responded, of whom 8,611 resided in the Netherlands (stage III), 604 in Germany (stage III), and 581 in Italy (stage IV). An additional 1,365 respondents completed the survey in the following week. Results: Participants indicated support for governmental measures related to avoiding social gatherings, selective closure of public places, and hand hygiene and respiratory measures (range for all measures: 95.0%-99.7%). Respondents from the Netherlands were less likely to consider a complete social lockdown effective (59.2%), compared to respondents in Germany (76.6%) or Italy (87.2%). Italian residents did not only apply enforced social distancing measures more frequently (range: 90.2%-99.3%, German and Dutch residents: 67.5%-97.0%), but also self-initiated hygienic and social distancing behaviors (range: 36.3%-96.6%, German and Dutch residents: 28.3%-95.7%). Respondents largely reported being sufficiently informed about the COVID-19 outbreak and about behaviors to avoid infection (range across countries: 90.2%-91.1%). Information channels most commonly reported included television (range: 53.0%-82.0%), newspapers (range: 31.0%-63.0%), official health websites (range: 39.0%-54.1%), and social media (range: 40.0%-55.8%). We observed no major changes in answers over time. Conclusions: In European countries, the degree of public belief in the effectiveness of protective measures was high and residents reported to be sufficiently informed by various communication channels. In March 2020, implementation of enacted and self-initiated measures differed between countries and were highest among Italian respondents, who were subjected to the most elaborate measures of social lockdown and greatest COVID-19 burden in Europe.


title: Fact-checking as risk communication: the multi-layered risk of misinformation in times of COVID-19

text: The emergence of the 2019 novel coronavirus has led to more than a pandemic—indeed, COVID-19 is spawning myriad other concerns as it rapidly marches around the globe. One of these concerns is a surge of misinformation, which we argue should be viewed as a risk in its own right, and to which insights from decades of risk communication research must be applied. Further, when the subject of misinformation is itself a risk, as in the case of COVID-19, we argue for the utility of viewing the problem as a multi-layered risk communication problem. In such circumstances, misinformation functions as a meta-risk that interacts with and complicates publics’ perceptions of the original risk. Therefore, as the COVID-19 “misinfodemic” intensifies, risk communication research should inform the efforts of key risk communicators. To this end, we discuss the implications of risk research for efforts to fact-check COVID-19 misinformation and offer practical recommendations.


A controversial debate: Vertical transmission of COVID-19 in pregnancy


title: Characteristics of SARS-CoV-2 positive and complicated COVID-19 patient cohorts in Israel: A comparative analysis

text: Reliably identifying patients at increased risk for COVID-19 complications could guide clinical decisions, public health policies, and preparedness efforts. The most globally accepted definitions of at-risk patients rely, primarily, on epidemiological characterization of hospitalized COVID-19 patients. However, such characterization overlooks, and fails to correct for, the prevalence of existing conditions in the wider SARS-CoV-2 positive population. Here, we use the complete medical records of 4,353 Israeli SARS-CoV-2 positive individuals, of whom 173 experienced moderate or severe symptoms of COVID-19, to identify the conditions that increase the risk of disease complications, in various age and sex strata. Our analysis suggests that cardiovascular and kidney diseases, obesity, and hypertension are significant risk factors for COVID-19 complications, as previously reported. Interestingly, it also indicates that depression (e.g., odds ratio, OR, for males 65 years or older: 2.94, 95% confidence intervals [1.55, 5.58]; P-value = 0.014) as well cognitive and neurological disorder (e.g., OR for individuals [≥] 65 year old: 2.65 [1.69, 4.17]; P-value < 0.001) are significant risk factors; and that smoking and background of respiratory diseases do not significantly increase the risk of complications. Adjusting existing risk definitions following these observations may improve their accuracy and impact the global pandemic containment efforts.


title: Adding the missing sugars to coronavirus protein structures

text: Protein structures solved by cryo-electron microscopy (cryo-EM) or X-ray crystallography often miss the sugar molecules known as glycans that cover large swaths of the proteins’ surfaces The recently reported structures of the spike protein on SARS-CoV-2, the novel coronavirus that causes COVID-19, are no different Researchers are now working to fill in some of those sugary blanks to better understand the virus’s biology and to help drugmakers develop vaccines and treatments “People usually go for what they can analyze” and focus mostly on the protein components of a structure, says Andrea Thorn, a structural biologist at the Julius Maximilian University of Würzburg She is a member of the Coronavirus Structural Task Force, a group of scientists who specialize in modeling and processing crystallographic and cryo-EM data Because structural biology measurements don’t reveal much about glycans on proteins, “we often fail to recognize what an important part of the structure they


title: A Computational Model for Estimating the Evolution of COVID-19 in Rondenia-Brazil

text: In this work, the modified SEIR model was proposed to account separately for the tested and isolated cases, with severe and critical symptoms, from those not tested, with mild and moderate symptoms. Two parameters were estimated and evaluated for the cases registered in Rondenia-Brazil, between March 20 and April 22. The basic reproduction rate did not remain constant during the period, showing variations eventually due to social behavior. The results show that the increase in the proportion of testing to about 56% provided a significant decrease in the confirmed cases since the expansion of the tested cases beyond the current testing criterion (20%) would help to identify and isolate also mild and moderate cases, generally referred to as asymptomatic.


title: The impact of early scientific literature in response to COVID-19: a scientometric perspective

text: Background. In the early phases of a new pandemic, identifying the most relevant evidence and quantifying which studies are shared the most can help researchers and policy makers. The aim of this study is to describe and quantify the impact of early scientific production in response to COVID-19 pandemic. Methods. The study consisted of: 1) review of the scientific literature produced in the first 30 days since the first COVID-19 paper was published; 2) analysis of papers' metrics with the construction of a Computed-Impact-Score (CIS) that represents a unifying score over heterogeneous bibliometric indicators. In this study we use metrics and alternative metrics collected into five separate categories. On top of those categories we compute the CIS. Highest CIS papers are further analyzed. Results. 239 papers have been included in the study. The mean of citations, mentions and social media interactions resulted in 1.63, 10 and 1250, respectively. The paper with highest CIS resulted "Clinical features of patients[...]" by Chaolin Huang et al., which rated first also in citations and mentions. This is the first paper describing patients affected by the new disease and reporting data that are clearly of great interest to both the scientific community and the general population. Conclusions. The early response of scientific literature during an epidemic does not follow a pre- established pattern. Being able to monitor how communications spread from the scientific world toward the general population using both traditional and alternative metric measures is essential, especially in the early stages of a pandemic.


title: Viral Induced Genetics Revealed by Multi-Dimensional Precision Medicine Transcriptional Workflow

text: Precision medicine requires the translation of basic biological understanding to medical insights, mainly applied to characterization of each unique patient. In many clinical settings, this requires tools that can be broadly used to identify pathology and risks. Patients often present to the intensive care unit with broad phenotypes, including multiple organ dysfunction syndrome (MODS) resulting from infection, trauma, or other disease processes. Etiology and outcomes are unique to individuals, making it difficult to cohort patients with MODS, but presenting a prime target for testing/developing tools for precision medicine. Using multi-time point whole blood (cellular/acellular) total transcriptomics in 27 patients, we highlight the promise of simultaneously mapping viral/bacterial load, cell composition, tissue damage biomarkers, balance between syndromic biology vs. environmental response, and unique biological insights in each patient using a single platform measurement. Integration of a transcriptome workflow yielded unexpected insights into the complex interplay between host genetics and viral/bacterial specific mechanisms, highlighted by a unique case of virally induced genetics (VIG) within one of these 27 patients. The power of RNAseq to study unique patient biology while investigating environmental contributions can be a critical tool moving forward for translational sciences applied to precision medicine.


title: COVID-19: Open-data resources for monitoring, modeling, and forecasting the epidemic

text: We provide an insight into the open-data resources pertinent to the study of the spread of the Covid-19 pandemic and its control. We identify the variables required to analyze fundamental aspects like seasonal behavior, regional mortality rates, and effectiveness of government measures. Open-data resources, along with data-driven methodologies, provide many opportunities to improve the response of the different administrations to the virus. We describe the present limitations and difficulties encountered in most of the open-data resources. To facilitate the access to the main open-data portals and resources, we identify the most relevant institutions, on a global scale, providing Covid-19 information and/or auxiliary variables (demographics, mobility, etc.). We also describe several open resources to access Covid-19 datasets at a country-wide level (i.e., China, Italy, Spain, France, Germany, US, etc.). To facilitate the rapid response to the study of the seasonal behavior of Covid-19, we enumerate the main open resources in terms of weather and climate variables. We also assess the reusability of some representative open-data sources.


title: Tafenoquine inhibits replication of SARS-Cov-2 at pharmacologically relevant concentrations in vitro

text: Tafenoquine [TQ] exhibited EC50/90s of ~ 2.6/5.1 μM against SARS-CoV-2 in VERO E6 cells and was 4-fold more potent than hydroxychloroquine [HCQ]. Time-of-addition experiments were consistent with a different mechanism for TQ v HCQ. Physiologically based pharmacokinetic (PBPK) modeling suggested that lung unbound concentrations of TQ in COVID-19 patients may exceed the EC90 for at least 8 weeks after administration. The therapeutic potential for TQ in management of COVID-19 should be further evaluated.


title: Investigating spatial variability in COVID-19 pandemic severity across 19 geographic areas, Spain, 2020

text: Background: Spain has been disproportionately affected by the COVID-19 pandemic with the second highest death toll in the world after Italy. Here we analyzed estimates of pandemic severity and investigated how different factors shaped the severity of the COVID-19 pandemic. Methods: We retrieved the daily cumulative numbers of laboratory-confirmed COVID-19 cases and deaths in Spain from February 20, 2020 to April 2, 2020. We used statistical methods to estimate the time-delay adjusted case fatality ratio (CFR) for 17 autonomous areas and 2 autonomous cities of Spain. We then assessed how transmission and sociodemographic variables were associated with the CFR across areas in Spain using multivariate regression analysis. Results: We estimated the highest time-delay-adjusted CFR for Madrid (38.4%) and the average adjusted CFR in Spain at 23.9%. Our multivariate regression analysis revealed a statistically significant three predictor variables: infant mortality rate, poverty risk rate and the cumulative morbidity rate. Conclusions: Our estimates of the time-delay adjusted CFR for 12 autonomous areas/cities in Spain are significantly higher than those previously estimated for other geographic regions including China and Korea. Our results call for urgent public health interventions focusing on low socioeconomic groups to ameliorate the burden of the COVID-19 pandemic in Spain.


title: Hypertension and Diabetes Delay the Viral Clearance in COVID-19 Patients

text: Objectives: Comorbidities have significant indications for the disease outcome of COVID-19, however which underlying diseases that contribute the most to aggravate the conditions of COVID-19 patients is still largely unknown. SARS-CoV-2 viral clearance is a golden standard for defining the recovery of COVID-19 infections. To dissect the underlying diseases that could impact on viral clearance, we enrolled 106 COVID-19 patients who were hospitalized in the Zhongnan Hospital of Wuhan University, Wuhan, China between Jan 5 and Feb 25, 2020. Methodology: We comprehensively analyzed demographic, clinical and laboratory data, as well as patient treatment records. Survival analyses with Kaplan-Meier and Cox regression modelling were employed to identify factors influencing the viral clearance negatively. Results: We found that increasing age, male gender, and angiotensin-converting enzyme 2 (ACE2) associated factors (including hypertension, diabetes, and cardiovascular diseases) adversely affected the viral clearance. Furthermore, analysis by a random forest survival model pointed out hypertension, cortisone treatment, gender, and age as the four most important variables. Conclusions: We conclude that patients at old age, males, and/or having diseases associated with high expression of ACE2 will have worse prognosis during a COVID-19 infections.


title: Children are unlikely to have been the primary source of household SARS-CoV-2 infections

text: BACKGROUND: Since its identification on the 7th of January 2020, SARS-CoV-2 has spread to more than 180 countries worldwide, causing >11,000 deaths. At present, viral disease and transmission amongst children is incompletely understood. Specifically, there is concern that children could be an important source of SARS-CoV-2 in household transmission clusters. METHODS: We performed an observational study analysing literature published between December 2019 and March 2020 of the clinical features of SARS-CoV-2 in children and descriptions of household transmission clusters of SARS-CoV-2. In these studies the index case of each cluster defined as the individual in the household cluster who first developed symptoms. FINDINGS: Drawing on studies from China, Singapore, South Korea, Japan, and Iran a broad range of clinical symptoms were observed in children. These ranged from asymptomatic to severe disease. Of the 31 household transmission clusters that were identified, 9.7% (3/31) were identified as having a paediatric index case. This is in contrast other zoonotic infections (namely H5N1 influenza virus) where 54% (30/56) of transmission clusters identified children as the index case. INTERPRETATION: Whilst SARS-CoV-2 can cause mild disease in children, the data available to date suggests that children have not played a substantive role in the intra-household transmission of SARS-CoV-2.


The role of pre-existing chronic disease in cardiac complications from SARS-CoV-2 infection: A systematic review and meta-analysis


title: IKONOS: An intelligent tool to support diagnosis of Covid-19 by texture analysis of x-ray images

text: In late 2019, the SARS-Cov-2 spread worldwide. The virus has high rates of proliferation and causes severe respiratory symptoms, such as pneumonia. There is still no specific treatment and diagnosis for the disease. The standard diagnostic method for pneumonia is chest X-ray image. There are many advantages to using Covid-19 diagnostic X-rays: low cost, fast and widely available. We propose an intelligent system to support diagnosis by X-ray images.We tested Haralick and Zernike moments for feature extraction. Experiments with classic classifiers were done. Support vector machines stood out, reaching an average accuracy of 89:78%, average recall and sensitivity of 0:8979, and average precision and specificity of 0:8985 and 0:9963 respectively. The system is able to differentiate Covid-19 from viral and bacterial pneumonia, with low computational cost.


title: Navigating Chemical Space By Interfacing Generative Artificial Intelligence and Molecular Docking

text: Here we report the testing and application of a simple, structure-aware framework to design target-specific screening libraries for drug development. Our approach combines advances in generative artificial intelligence (AI) with conventional molecular docking to rapidly explore chemical space conditioned on the unique physiochemical properties of the active site of a biomolecular target. As a proof-of-concept, we used our framework to construct a focused library for cyclin-dependent kinase type-2 (CDK2). We then used it to rapidly generate a library specific to the active site of the main protease (Mpro) of the SARS-CoV-2 virus, which causes COVID-19. By comparing approved and experimental drugs to compounds in our library, we also identified six drugs, namely, Naratriptan, Etryptamine, Panobinostat, Procainamide, Sertraline, and Lidamidine, as possible SARS-CoV-2 Mpro targeting compounds and, as such, potential drug repurposing candidates. To complement the open-science COVID-19 drug discovery initiatives, we make our SARS-CoV-2 Mpro library fully accessible to the research community (https://github.com/atfrank/SARS-CoV-2).


title: SARS-CoV-2 targets cortical neurons of 3D human brain organoids and shows neurodegeneration-like effects

text: COVID-19 pandemic caused by SARS-CoV-2 infection is a public health emergency. COVID-19 typically exhibits respiratory illness. Unexpectedly, emerging clinical reports indicate that neurological symptoms continue to rise, suggesting detrimental effects of SARS-CoV-2 on the central nervous system (CNS). Here, we show that a Düsseldorf isolate of SARS-CoV-2 enters 3D human brain organoids within two days of exposure. Using COVID-19 convalescent serum, we identified that SARS-CoV-2 preferably targets soma of cortical neurons but not neural stem cells, the target cell type of ZIKA virus. Imaging cortical neurons of organoids reveal that SARS-CoV-2 exposure is associated with missorted Tau from axons to soma, hyperphosphorylation, and apparent neuronal death. Surprisingly, SARS-CoV-2 co-localizes specifically with Tau phosphorylated at Threonine-231 in the soma, indicative of early neurodegeneration-like effects. Our studies, therefore, provide initial insights into the impact of SARS-CoV-2 as a neurotropic virus and emphasize that brain organoids could model CNS pathologies of COVID-19. One sentence summary COVID-19 modeling in human brain organoids


title: Corporate communication, public relations and reputational risk management in the days of covid-19/ Comunicación corporativa, relaciones públicas y gestión del riesgo reputacional en tiempos del covid-19

text: The Covid-19 crisis has put to the test many social structures processes. Corporate communication and public relations are examples of these processes that face an unprecedented situation, difficult to foresee and from which lessons will have to be drawn for the future. In this article, a mixture of research and essay, we intend, based on theory, and on the experience and some studies carried out by communication professionals as well, to reflect on how the pandemic crisis of the Covid-19 affects and will condition the practice of corporate communication in general and two of its areas of specialization, internal communication and corporate social responsibility (CSR). We emphasize the importance of organizations in assuming that reputation is a risk and that this risk must be managed with public relations tactics and tools, because the pandemic crisis of the so-called coronavirus has revealed the importance for organizations and brands of managing trustworthy relationships with their publics.


title: Pooling RT-PCR test of SARS-CoV-2 for large cohort of 'healthy' and infection-suspected patients: A prospective and consecutive study on 1,000 individuals

text: Background SARS-CoV-2 testing reagents are expected to become in short supply worldwide. However, little is unknown whether the pooling strategy detects SARS-CoV-2 with accuracy. Method To validate the feasibility of pooling samples, serial dilution analysis and spike-in experiment were conducted using synthetic DNA and nucleic acids extracted from SARS-CoV-2 positive and negative patients. Furthermore, we studied a total of 1,000 individuals, who were 667 'healthy' (195 healthcare workers and 472 hospitalized patients with other disorders than COVID-19 infection) individuals and 333 infection-suspected patients with cough and fever, were tested. Results Serial dilution analysis showed the limit of detection of around 10-100 copies according to National Institute of Infectious Diseases, Japan. Spike-in experiment demonstrated RT-qPCR detect positive signal in pooling samples of SARS-CoV-2 negative and positive patient at the 5-, 10-, 20-fold dilution. By screening with pooling strategy by the end of April, 2020, there are 12 COVID-19 patients in 333 infection suspected patients (3.6%) and zero in 667 'healthy'. We obtained these results with total running 538 times (instead of 1,000 times) by pooling strategy. Conclusion Pooling samples is feasible for saving test reagents and detecting SARS-CoV-2 in clinical setting to prevent the spread of the virus and nosocomial transmission.


title: Gap junction internalization and processing in vivo: a 3D immuno-electron microscopy study

text: Gap junctions have well-established roles in cell-cell communication by way of forming permeable intercellular channels. Less is understood about their internalization, which forms double membrane vesicles containing cytosol and membranes from another cell, called connexosomes or annular gap junctions. Here, we systematically studied the fate of connexosomes in intact ovarian follicles. High pressure frozen, serial sectioned tissue was immunogold labeled for Connexin 43. Within a volume of electron micrographs, every labeled structure was categorized and counted. Surface area measurements indicate that large connexosomes undergo fission. Subsequent modifications are separation of inner and outer membranes, loss of Cx43 from the outer membrane, and outward budding of the modified membranes. We also documented several clear examples of organelle transfer from one cell to another by gap junction internalization. We discuss how connexosome formation and processing may be a novel means for gap junctions to mediate cell-cell communication.


title: Topological Analysis of SARS CoV-2 Main Protease

text: There is an urgent necessity of effective medication against SARS CoV-2, which is producing the COVID-19 pandemic across the world. Its main protease (Mpro) represents an attractive pharmacological target due to its involvement in essential viral functions. The crystal structure of free Mpro shows a large structural resemblance with the main protease of SARS CoV (nowadays known as SARS CoV-1). Here we report that as average SARS CoV-2 Mpro is 1900% more sensitive than SARS CoV-1 Mpro in transmitting tiny structural changes across the whole protein through long-range interactions. The largest sensitivity of Mpro to structural perturbations is located exactly around the catalytic site Cys-145, and coincides with the binding site of strong inhibitors. These findings, based on a simplified representation of the protein as a residue network, may help in designing potent inhibitors of SARS CoV-2 Mpro. The main protease of the new coronavirus SARS CoV-2 represents one of the most important targets for the antiviral pharmacological actions againsts COVID-19. This enzyme is essential for the virus due to its proteolytic processing of polyproteins. Here we discover that the main protease of SARS CoV-2 is topologically very similar to that of the SARS CoV-1. This is not surprising taking into account that both proteases differ only in 12 amino acids. However, we remarkable found a topological property of SARS CoV-2 that has increased in more than 1900% repect to its SARS CoV-1 analogue. This property reflects the capacity of the new protease of transmitting perturbations across its domains using long-range interactions. Also remarkable is the fact that the amino acids displaying such increased sensitivity to perturbations are around the binding site of the new protease, and close to its catalytic site. We also show that this sensititivy to perturbations is related to the effects of powerful protease inhibitors. In fact, the strongest inhibitors of the SARS CoV-2 main protease are those that produce the least change of this capacity of transmitting perturbations across the protein. We think that these findings may help in the design of new potent anti-SARS CoV-2 inhibitors.


title: Genetic information insecurity as state of the art

text: Genetic information is being generated at an increasingly rapid pace, offering advances in science and medicine that are paralleled only by the threats and risk present within the responsible ecosystem. Human genetic information is identifiable and contains sensitive information, but genetic data security is only recently gaining attention. Genetic data is generated in an evolving and distributed cyber-physical ecosystem, with multiple systems that handle data and multiple partners that utilize the data. This paper defines security classifications of genetic information and discusses the threats, vulnerabilities, and risk found throughout the entire genetic information ecosystem. Laboratory security was found to be especially challenging, primarily due to devices and protocols that were not designed with security in mind. Likewise, other industry standards and best practices threaten the security of the ecosystem. A breach or exposure anywhere in the ecosystem can compromise sensitive information. Extensive development will be required to realize the potential of this emerging field while protecting the bioeconomy and all of its stakeholders.


title: A case-control and cohort study to determine the relationship between ethnic background and severe COVID-19

text: Background. People of minority ethnic background may be disproportionately affected by severe COVID-19 for reasons that are unclear. We sought to examine the relationship between ethnic background and (1) hospital admission for severe COVID-19; (2) in-hospital mortality. Methods. We conducted a case-control study of 872 inner city adult residents admitted to hospital with confirmed COVID-19 (cases) and 3,488 matched controls randomly sampled from a primary healthcare database comprising 344,083 people resident in the same region. To examine in-hospital mortality, we conducted a cohort study of 1827 adults consecutively admitted with COVID-19. Data collected included hospital admission for COVID-19, demographics, comorbidities, in-hospital mortality. The primary exposure variable was self-defined ethnicity. Results. The 872 cases comprised 48.1% Black, 33.7% White, 12.6% Mixed/Other and 5.6% Asian patients. In conditional logistic regression analyses, Black and Mixed/Other ethnicity were associated with higher admission risk than white (OR 3.12 [95% CI 2.63-3.71] and 2.97 [2.30- 3.85] respectively). Adjustment for comorbidities and deprivation modestly attenuated the association (OR 2.28 [1.87-2.79] for Black, 2.66 [2.01-3.52] for Mixed/Other). Asian ethnicity was not associated with higher admission risk (OR 1.20 [0.86-1.66]). In the cohort study of 1827 patients, 455 (28.9%) died over a median (IQR) of 8 (4-16) days. Age and male sex, but not Black (adjusted HR 0.84 [0.63-1.11]) or Mixed/Other ethnicity (adjusted HR 0.69 [0.43-1.10]), were associated with in-hospital mortality. Asian ethnicity was associated with higher in-hospital mortality (adjusted HR 1.54 [0.98-2.41]). Conclusions. Black and Mixed ethnicity are independently associated with greater admission risk with COVID-19 and may be risk factors for development of severe disease. Comorbidities and socioeconomic factors only partly account for this and additional ethnicity-related factors may play a large role. The impact of COVID-19 may be different in Asians.


title: Class I HLA allele restricted antigenic coverage for Spike and N proteins is associated with divergent outcomes for COVID-19

text: The world is dealing with the worst pandemics ever. SARS-CoV-2 is the etiological agent of COVID-19 that has already spread to more than 200 countries. However, infectivity, severity and mortality rates do not affect all countries equally. Here we investigate the landscape of potential HLA-I A and B restricted SARS-CoV-2-derived antigens and how different populations in the world are predicted to respond to those peptides considering their HLA-I distribution frequencies. Clustering of HLA-A and HLA-B allele frequencies partially separates most countries with the lowest number of deaths per million inhabitants from the other countries. We further correlated the patterns of in silico predicted strong binder peptides and epidemiological data. The number of deaths per million inhabitants inversely correlated with the antigen coverage of peptides derived from viral protein S, while a direct correlation was observed for those derived from viral protein N, highlighting a potential risk group carrying HLAs associated with the latter. In addition, we identified 7 potential antigens bearing at least one amino acid of the small insertion that differentiates SARS-CoV-2 from previous coronavirus strains. We believe these data can contribute to the search for peptides with the potential to be used in vaccine strategies.


Virus masks a different threat: China is using Covid-19 responses and Hong Kong’s new security law to reduce freedoms in the city state


title: Phylodynamics of SARS-CoV-2 transmission in Spain

text: Objectives SARS-CoV-2 whole-genome analysis has identified three large clades spreading worldwide, designated G, V and S. This study aims to analyze the diffusion of SARS-CoV-2 in Spain/Europe. Methods Maximum likelihood phylogenetic and Bayesian phylodynamic analyses have been performed to estimate the most probable temporal and geographic origin of different phylogenetic clusters and the diffusion pathways of SARS-CoV-2. Results Phylogenetic analyses of the first 28 SARS-CoV-2 whole genome sequences obtained from patients in Spain revealed that most of them are distributed in G and S clades (13 sequences in each) with the remaining two sequences branching in the V clade. Eleven of the Spanish viruses of the S clade and six of the G clade grouped in two different monophyletic clusters (S-Spain and G-Spain, respectively), with the S-Spain cluster also comprising 8 sequences from 6 other countries from Europe and the Americas. The most recent common ancestor (MRCA) of the SARS-CoV-2 pandemic was estimated in the city of Wuhan, China, around November 24, 2019, with a 95% highest posterior density (HPD) interval from October 30-December 17, 2019. The origin of S-Spain and G-Spain clusters were estimated in Spain around February 14 and 18, 2020, respectively, with a possible ancestry of S-Spain in Shanghai. Conclusions Multiple SARS-CoV-2 introductions have been detected in Spain and at least two resulted in the emergence of locally transmitted clusters, with further dissemination of one of them to at least 6 other countries. These results highlight the extraordinary potential of SARS-CoV-2 for rapid and widespread geographic dissemination.


title: The coronavirus disease 2019 (COVID-19) pandemic: A review and an update on cases in Africa

text: The world has experienced several epidemics posing serious threat to global public health, including the 2002 severe acute respiratory syndrome (SARS) epidemic that caused 800 deaths out of about 8 000 cases, the 2009 H1N1 pandemic with 18 500 deaths, the 2012 Middle East respiratory syndrome (MERS) epidemic that caused 800 deaths out of 2 500 cases, the 2014 Ebola outbreak with 28 616 cases and 11 310 deaths, and the current coronavirus disease (COVID-19) pandemic with more than 35 000 deaths out of over 730 000 confirmed cases till now. Emerging infectious diseases continue to infect and reduce human populations. The COVID-19 pandemic has spread to more than 114 countries before it was officially declared as a pandemic by the WHO on the 11thMarch 2020. Here, the first set of index cases in Africa, and the differences between SARS-CoV-2 and other coronaviruses in addition to the preventive strategies on the emergence of COVID-19 were reviewed.


title: National estimates of critical care capacity in 54 African countries.

text: Background The coronavirus disease (COVID-19) pandemic is an emerging threat across the African continent where national critical care capacity is underdeveloped or unknown. In this paper, we compile data on critical care capacity -- including number of ICU beds, number of ventilators, and number of physician and non-physician anesthesia providers -- for 54 African countries. Methods Data was compiled from a variety of resources including World Bank databases, local and international news media, government reports, local healthcare workers, and published scientific literature. Results Overall, data on number of ICU beds were available for 49 (91%) countries and on number of ventilators for 46 (85%) countries, respectively. Data on physician anesthesia providers and non-physician providers was available for 47 (87%) and 37 (69%) of the 54 African countries. Conclusion Most low and lower middle-income African countries have limited critical care capacity available to cope with potential surges in critical care demand due to COVID-19 outbreaks. Keywords: COVID-19, SARS-CoV-2, critical care capacity, ICU, ventilators, Africa


title: Research Resiliency through Lean Labs

text: Academic research groups, especially the ones directed by new junior faculty are under pressure to produce high-quality work timely while constrained by limited budget, resources, and lab space A well-organized lab is crucial for a wide range of reasons, from keeping costs low, to protecting the health and safety of users The focus herein is on developing lab-level systems that create a lean and productive space in the context of academic cleanrooms The efforts made at implementing the 5S organizational methodology to improve cleanroom functions, including regulatory compliance, organization, and resource stewardship, is described The quantifiable result is that chemical consumption spending is reduced by 41%, between 2018 and 2019, whereas materials consumption spending is reduced by 52% Meanwhile, there is a 116% increase in the number of fabricated devices, showing greater output using less resources This management system also proved itself to be beneficial during emergency situations The recent COVID-19 pandemic is one such instance that showcased the ability to systematically ramp-down operations within 15?min, taking a huge burden away from the research group, and thus allowing to focus on what is most important during this time of crisis: the health and safety of the group and community


title: Is scaling-up COVID-19 testing cost-saving?

text: The World Health Organization currently recommends that governments scale up testing for COVID-19 infection. We performed health economic analyses projecting whether the additional costs from screening would be offset by the avoided costs with hospitalizations. We analysed Portuguese COVID-19 data up until the 22nd March 2020, and estimated the additional number of cases that would be detected if different testing rates and frequencies of positive results would have been observed. We projected that, in most scenarios, the costs with scaling up COVID-19 tests would be lower than savings with hospitalization costs, rendering large scale testing cost-saving.


title: Kidney and Lung ACE2 expression after an ACE inhibitor or an Ang II receptor blocker: implications for COVID-19

text: Background There have been concerns that ACE inhibitors and Ang II receptor blockers may cause an increase in ACE2, the main receptor for SARs-CoV-2. Methods Kidneys from two genetic models of kidney ACE ablation and mice treated with captopril or telmisartan were used to examine ACE2 in isolated kidney and lung membranes. Results In a global ACE KO mice, ACE2 protein abundance in kidney membranes was reduced to 42 % of wild type, p < 0.05. In ACE 8/8 mice that over-expresses cardiac ACE protein but also has no kidney ACE expression, ACE2 protein in kidney membranes was also decreased (38 % of the WT, p<0.01). In kidney membranes from mice that received captopril or telmisartan for 2 weeks there was a reduction in ACE2 protein (37% in captopril treated p<0.01) and 76% in telmisartan treated p <0.05). In lung membranes the expression of ACE2 was very low and not detected by western blotting but no significant differences in terms of ACE2 activity could be detected in mice treated with captopril (118% of control) or telmisartan (93% of control). Conclusions Genetic kidney ACE protein deficiency, suppressed enzymatic activity by Captopril or blockade of the AT1 receptor with telmisartan are all associated with a decrease in ACE2 in kidney membranes. ACE2 protein in kidney or lungs is decreased or unaffected by RAS blockers indicating that these medications can not pose a risk for SARS-CoV-2 infection related to amplification of ACE2 at these two target sites for viral entry.


Neglected major causes of death much deadlier than COVID-19


title: Assessment of respiratory droplet transmission during the ophthalmic slit lamp exam: a particle tracking analysis

text: Purpose: The global COVID-19 pandemic has resulted in a renewed focus on the importance of personal protective equipment (PPE) and other interventions to decrease spread of infectious diseases. While several ophthalmology organizations have released guidance on appropriate PPE for surgical procedures and ophthalmology clinics, there is limited experimental evidence demonstrating the efficacy of various interventions that have been suggested. In this study, we evaluate high-risk aspects of the slit-lamp exam and the effect of various PPE interventions. Design: Experimental cough simulation using a fluorescent surrogate of respiratory droplets during an ophthalmic slit lamp examination. Methods: Setting: Single-center Study Population: Patient Simulation Main outcome measure(s): Presence of fluorescent particles in the air near or on slit lamp and simulated slit lamp examiner. Results: Simulated coughing without a mask or slit lamp shield resulted in widespread dispersion of fluorescent droplets during the model slit lamp examination. Coughing with a mask resulted in the most significant decrease in droplets, however, particles still escaped from the top of the mask. Coughing with the slit lamp shield alone blocked most of forward particle dispersion; however significant distributions of respiratory droplets were found on the slit lamp joystick and table. Coughing with both mask and slit lamp shield resulted in the least dispersion to the simulated examiner. Scanning electron microscopy demonstrated particle sizes of 3-100m. Conclusions: Masking has the greatest effect in limiting spread of respiratory droplets, while slit lamp shields and gloves also contribute to limiting exposure to droplets from SARS-CoV-2 during slit lamp examination.


title: Design and rationale of the Longitudinal Evaluation of Norms and Networks Study (LENNS): A cluster-randomized trial assessing the impact of a norms-centric intervention on exclusive toilet use and maintenance in peri-urban communities of Tamil Nadu

text: Introduction: Inconsistent toilet usage is a continuing challenge in India. Despite the impact of social expectations on toilet usage, few programs and studies have developed theoretically grounded norms-centric behavior change interventions to increase toilet use in low-income settings. This protocol details the rationale and design of an ex-ante, parallel cluster-randomized trial evaluating the impact of a demand-side, norms-centric behavior change intervention on exclusive toilet use and maintenance in peri-urban Tamil Nadu, India. Methods and Analysis: Following two years of formative research, we developed an evidence-based norm-centric behavior change intervention called Nam Nalavazhvu (Tamil for 'Our wellbeing'). The multi-level intervention aims to shift collective beliefs by shifting empirical expectations or beliefs about other relevant people's sanitation practices. It also provides action-oriented information to aid individuals to set goals and overcome barriers to build, consistently use and maintain their toilets. This trial includes 76 wards in Pudukkottai and Karur districts, where half were randomly assigned to receive the intervention and the remaining serve as counterfactuals. During baseline and endline (conducted one year after the initiation of intervention) assessments, we collect relevant data and compare results between study arms to determine the impacts of the Nam Nalavazhvu intervention on sanitation-related behavioral, health, wellbeing outcomes and potential moderators. This study is powered to detect differences in the prevalence of exclusive toilet use between study arms. We will also conduct a process evaluation to understand the extent to which the intervention was implemented, as designed.


title: A fractional-order SEIHDR model for COVID-19 with inter-city networked coupling effects

text: A novel coronavirus, designated as COVID-19, e-merged in Wuhan, China, at the end of 2019. In this paper, a mathematical model is proposed to analyze the dynamic behavior of COVID-19. Based on inter-city networked cou-pling effects, a fractional-order SEIHDR system with the real-data from 23 January to 18 March, 2020 of COVID-19 is discussed. Meanwhile, hospitalized individuals and the mortality rates of three types of individuals (exposed, in-fected and hospitalized) are firstly taken into account in the proposed model. And infectivity of individuals during in-cubation is also considered in this paper. By applying least squares method and predictor-correctors scheme, the numer-ical solutions of the proposed system in the absence of the inter-city network and with the inter-city network are stim-ulated by using the real-data from 23 January to 18 - m March, 2020 where m is equal to the number of predic-tion days. Compared with integer-order system ( = 0), the fractional-order model without network is validated to have a better fitting of the data on Beijing, Shanghai, Wuhan, Huanggang and other cities. In contrast to the case with-out network, the results indicate that the inter-city network system may be not a significant case to virus spreading for China because of the lock down and quarantine measures, however, it may have an impact on cities that have not adopted city closure. Meanwhile, the proposed model better fits the data from 24 February to 31, March in Italy, and the peak number of confirmed people is also predicted by this fraction-order model. Furthermore, the existence and unique-ness of a bounded solution under the initial condition are considered in the proposed system. Afterwards, the basic re-production number R0 is analyzed and it is found to hold a threshold: the disease-free equilibrium point is locally asymp-totically stable when R0 [≤] 1, which provides a theoretical basis for whether COVID-19 will become a pandemic in the future.


title: An optimal lockdown relaxation strategy for minimizing the economic effects of covid-19 outbreak in Sri Lanka

text: In order to recover the damage to the economy by the ongoing covid-19 pandemic, Sri Lanka is undergoing a gradual transition from strict lockdowns to partial lockdowns through relaxation of curfew and other moderated preventive measures. In this work, we propose an optimal lockdown relaxation strategy, which is aimed at minimizing the damage to the economy, while confining the covid-19 incidence to a level endurable by the available healthcare capacity in the country. The relevant optimization model turns out to be non-linear. We use the technique of separable programming to generate solutions and discuss the results.


title: Effectiveness of airport screening at detecting travellers infected with 2019-nCoV

text: As the number of novel coronavirus cases grows both inside and outside of China, public health authorities require evidence on the effectiveness of control measures such as thermal screening of arrivals at airports. We evaluated the effectiveness of exit and entry screening for 2019-nCoV infection. In our baseline scenario, we estimated that 46.5% (95%CI: 35.9 to 57.7) of infected travellers would not be detected, depending on the incubation period, sensitivity of exit and entry screening, and the proportion of cases which are asymptomatic. Airport screening is unlikely to detect a sufficient proportion of 2019-nCoV infected travellers to avoid entry of infected travellers. We developed an online tool so that results can be updated as new information becomes available.


title: Search for trends of Covid-19 infection in India, China, Denmark, Brazil, France. Germany and the USA on the basis of power law scaling

text: The corona virus (SARS-CoV-2) or Covid-19 pandemic is growing alarmingly throughout the whole world. Using the power law scaling we analyze the data of different countries and three states of India up to 1st April, 2020 and explain in terms of power law exponent. We find significant reduction in growth of infections in China and Denmark (g reduced from approximately 2.18 to 0.05 and 11.41 to 6.95, respectively). Very slow reduction is also seen in Brazil and Germany (g reduced from approximately 6 to 4 and 11 to 7, respectively). Infection in India is growing (g=9.23) though lesser in number than that in the USA (highest g of 16 approximately, studied so far), Italy and a few other countries. Among three Indian states the growth in West Bengal (g=0.64) is much slower than other states like Maharashtra and Kerala (g=3.23 and 3.32, respectively). Some future predictions, though not rigid, has also been incorporated in our analysis. The earlier lock-down and stricter measures from the Governments concerned are being thought to be the only possible solutions, in the present situation, to fight against this virus.


title: A cohort-based emergency plan to maintain functionality in a clinical laboratory during the 2020 COVID-19 epidemic outbreak

text: Objectives: Clinical laboratory analyses are essential part of critical care Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/coronavirus disease 2019 (COVID-19)-confirmed cases were doubling in Germany every 3 days during March 2020 Health care systems are preparing for an epidemic crisis Methods: We outline a cohort-based emergency planning The plan is based on three independent self-sufficient cohorts that maintain duty for 7 days, followed by quarantine-like rest for 14 days COVID-19-infected and otherwise ill personnel will be replaced by a tactical reserve, which is again replaced by recovered staff Results: We switched to the outlined system when incidence of confirmed COVID-19 cases surpassed 50/100,000 residents Our parameter spectrum was reduced to the essential analyses in agreement with our clinical colleagues So far the system works well In model calculations, the system is robust to maintain essential laboratory functionality even when incidence of COVID-19 is higher than that currently observed in the most severely hit countries Conclusions: We outline a cohort-based emergency planning to maintain essential functionality of a clinical laboratory while minimizing the risk of spreading infection with COVID-19 among our workforce during the COVID-19 epidemic faced in 2020


title: Development of Real-time Diagnosis Framework for Angular Misalignment of Robot Spot-welding System Based on Machine Learning

text: Abstract This paper focuses on the real-time online monitoring and diagnosis framework for the angular misalignment of the robot spot-welding system, which can result in significant quality degradation of a weld nugget such as porosity. The data-driven approach is applied by installing the voltage and current sensors, collecting the associated mass data and processing them under normal and abnormal (angular misalignment) conditions. Two categories of features are extracted from the dynamic resistance (DR) and the voltage and current ones that are decomposed by wavelet transform (WT). The DR features are extracted from the DR profile and some critical features are selected by a t-test methodology. In the case of the WT-based features, the critical ones are selected by a max-relevance and min-redundancy (mRMR) and a sequential backward selection (SBS) wrapper. Consequently, three types of critical feature sets, such as DR features, WT features, and hybrid features combining those, are prepared to train machine learning-based models. Support vector machine (SVM) and probabilistic neural network (PNN) are applied to establish the diagnosis models, and the diagnostic accuracy and robustness are evaluated. Finally, the software for the on-line monitoring and diagnosis for angular misalignment of robot spot-welding system is developed and demonstrates its real-time applicability in an industrial site.


title: Mitigation and herd immunity strategy for COVID-19 is likely to fail

text: On the basis of a semi-realistic SIR microsimulation for Germany and Poland, we show that the R0 parameter interval for which the COVID-19 epidemic stays overcritical but below the capacity limit of the health care system to reach herd immunity is so narrow that a successful implementation of this strategy is likely to fail. Our microsimulation is based on official census data and involves household composition and age distribution as the main population structure variables. Outside household contacts are characterised by an out-reproduction number R* which is the only free parameter of the model. For a subcritical domain we compute the time till extinction and prevalence as a function of the initial number of infected individuals and R*. For the Polish city of Wroclaw we also discuss the combined impact of testing coverage and contact reduction. For both countries we estimate R* for disease progression until 20th of March 2020.


title: Solvable delay model for epidemic spreading: the case of Covid-19 in Italy

text: We present a simple but realistic model for describing the diffusion of an infectious disease on a population of individuals. The dynamics is governed by a single functional delay differential equation, which, in the case of a large population, can be solved exactly, even in the presence of a time-dependent infection rate. This delay model has a higher degree of accuracy than the so-called SIR model, commonly used in epidemiology, which, instead, is formulated in terms of a set of three ordinary differential equations. We apply our model to describe the outbreak of the new virus COVID-19 in Italy, taking into account the containment measures implemented by the government in order to mitigate the spreading of the virus and the social costs for the population.


title: Comprehensive in-vivo secondary structure of the SARS-CoV-2 genome reveals novel regulatory motifs and mechanisms

text: SARS-CoV-2 is the positive-sense RNA virus that causes COVID-19, a disease that has triggered a major human health and economic crisis. The genome of SARS-CoV-2 is unique among viral RNAs in its vast potential to form stable RNA structures and yet, as much as 97% of its 30 kilobases have not been structurally explored in the context of a viral infection. Our limited knowledge of SARS-CoV-2 genomic architecture is a fundamental limitation to both our mechanistic understanding of coronavirus life cycle and the development of COVID-19 RNA-based therapeutics. Here, we apply a novel long amplicon strategy to determine for the first time the secondary structure of the SARS-CoV-2 RNA genome probed in infected cells. In addition to the conserved structural motifs at the viral termini, we report new structural features like a conformationally flexible programmed ribosomal frameshifting pseudoknot, and a host of novel RNA structures, each of which highlights the importance of studying viral structures in their native genomic context. Our in-depth structural analysis reveals extensive networks of well-folded RNA structures throughout Orf1ab and reveals new aspects of SARS-CoV-2 genome architecture that distinguish it from other single-stranded, positive-sense RNA viruses. Evolutionary analysis of RNA structures in SARS-CoV-2 shows that several features of its genomic structure are conserved across beta coronaviruses and we pinpoint individual regions of well-folded RNA structure that merit downstream functional analysis. The native, complete secondary structure of SAR-CoV-2 presented here is a roadmap that will facilitate focused studies on mechanisms of replication, translation and packaging, and guide the identification of new RNA drug targets against COVID-19.


title: Cracking the code to the 2019 novel coronavirus (COVID-19): Lessons from the eye

text: With the recent March 11, 2020 declaration of a pandemic by the World Health Organization (WHO) further attention has turned to understanding and managing the outbreak of infectious disease termed coronavirus disease 2019 (COVID-19) caused by the novel coronavirus identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SARS-CoV-2 gains entry into human cells through its ability to bind to a human ACE2 protein. Through our understanding of diabetic retinopathy, there are genetic-based variations in ACE2 levels that confer varying risk profiles for diabetic retinopathy. Similarly, emerging research suggests ACE2 levels confer varying risk profiles for COVID-19- Using data comparisons between geographic prevalence rates of diabetic retinopathy and existing COVID-19 mortality rates may enable improved predictions of the rates of spread of COVID-19 in various geographic regions. The goal of this report is to encourage cross-disciplinary horizontal vision in the field of medicine and science in order to further progress in managing and treating human disease.


title: Comperative analysis and forecasting of COVID-19 cases in various European countries with ARIMA, NARNN and LSTM approaches

text: In this study, confirmed COVID-19 cases of Denmark, Belgium, Germany, France, United Kingdom, Finland, Switzerland and Turkey were modeled with Auto-Regressive Integrated Moving Average (ARIMA), Nonlinear Autoregression Neural Network (NARNN) and Long-Short Term Memory (LSTM) approaches. Six model performance metric were used to select the most accurate model (MSE, PSNR, RMSE, NRMSE, MAPE and SMAPE). According to the results of the first step of the study, LSTM was found the most accurate model. In the second stage of the study, LSTM model was provided to make predictions in a 14-day perspective that is yet to be known. Results of the second step of the study shows that the total cumulative case increase rate is expected to decrease slightly in many countries.


title: Sensitivity of UK Covid-19 deaths to the timing of suppression measures and their relaxation

text: In this paper I examine the sensitivity of total UK Covid-19 deaths and the demand for intensive care and ward beds, to the timing and duration of suppression periods during a 500 day period. This is achieved via a SEIR model. Using an expected latent period of 4.5 days and infectious period of 3.8 days, R_0 was first estimated as 3.18 using observed death rates under unmitigated spread and then under the effects of the total lock down (R_0=0.60) of 23 March. The case fatality rate given infection is taken as 1%. Parameter values for mean length of stay and conditional probability of death for ICU and non-ICU hospital admissions are guided by Ferguson et al.(2020). Under unmitigated spread the model predicts around 600,000 deaths in the UK. Starting with one exposed person at time zero and a suppression consistent with an R_0 of 0.60 on day 72, the model predicts around 39,000 deaths for a first wave, but this reduces to around 11,000 if the intervention takes place one week earlier. If the initial suppression were in place until day 200 and then relaxed to an R_0 of 1.5 between days 200 and 300, to be followed by a return to an R_0 of 0.60, the model predicts around 43,000 deaths. This would increase to around 48,000 if the release from the first suppression takes place one week earlier. The results indicate the extreme sensitivity to timing and the consequences of even small delays to suppression and premature relaxation of such measures.


COVID-19 Closes Labs, Slows Data Collection—The Impact on Neurology Research


title: A cytosine-to-uracil change within the programmed -1 ribosomal frameshift signal of SARS-CoV-2 results in structural similarities with the MERS-CoV signal

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of the ongoing COVID-19 pandemic, like many other viruses, uses programmed ribosomal frameshifting (PRF) to enable synthesis of multiple proteins from its compact genome. In independent analyses, we evaluated the PRF regions of all SARS-CoV-2 sequences available in GenBank and from the Global Initiative on Sharing All Influenza Data for variations. Of the 5,156 and 27,153 sequences analyzed, respectively, the PRF regions were identical in 95.7% and 97.2% of isolates. The most common change from the reference sequence was from C to U at position 13,536, which lies in the three-stemmed pseudoknot known to stimulate frameshifting. With the conversion of the G13493-C13536 Watson-Crick pair to G-U, the SARS-CoV-2 PRF closely resembles its counterpart in the Middle East respiratory syndrome coronavirus. The occurrence of this change increased from 0.5 to 3% during the period of March to May 2020.


Complicated myocardial infarction in a 99-year-old lady in the era of COVID-19 pandemic: from the need to rule out coronavirus infection to emergency percutaneous coronary angioplasty


title: Can judgments according to case fatality rate be correct all the time during epidemics? Estimated cases based on CFR in different scenarios and some lessons from early case fatality rate of coronavirus disease 2019 in Iran

text: Background: The new Coronavirus disease (COVID-19) was first identified in China in 2019. Case fatality rate (CFR) indicator of the disease is one of the most important indices noticed by experts, policymakers, and managers, based on which daily evaluations and many judgments are made. CFR can change during epidemics. This study aimed to estimate the actual number of COVID-19 cases in Iran and to calculate the early CFR for the disease based on official statistics. Methods: This was a descriptive study whose data were obtained from the website of the Ministry of Health and Medical Education of Iran from February 20, 2020 until March 26, 2020. CFR has been obtained by dividing the total number of deaths by the total number of confirmed cases at one point in time. In this study, the actual number of COVID-19 cases in Iran was estimated based on the mortality model in 4 scenarios. Excel 2013 software was used to analyze the data. Results: According to the findings of this study, In Iran, until March 26, 2020, a total of 27 017 people have been infected by COVID-19 and 2077 died of it. However, CFR indicator had a descending trend in Iran: 100%, 18.6%, 8.8%, 3.3%, 6.9%, and 7.7% on days 1, 5, 10, 20, 30, and 35, respectively. The actual number of COVID-19 cases in Iran was estimated to be 4 789 454, 2 873 673, 1 436 836, and 718418 as of March 26, 2020 according to the 4 scenarios, respectively. Conclusion: In emerging epidemics, CFR indicator must not be used as a basis to judge the performance of a health system unless that epidemic condition has been clarified. Moreover, it is suggested that in the outbreak of an epidemic, specifically emerging diseases, CFR must not be the base of judgment. Making judgments, specifically in the outbreak of emerging epidemics, based on fatality rate can lead to information bias. It is also possible to estimate the total number of patients based on the CFR in circumstances where little information is available on the disease.


Special Coverage on COVID-19: History Matters—for Influenza and COVID-19


title: RNAVLab: A virtual laboratory for studying RNA secondary structures based on grid computing technology

text: Abstract As ribonucleic acid (RNA) molecules play important roles in many biological processes including gene expression and regulation, their secondary structures have been the focus of many recent studies. Despite the computing power of supercomputers, computationally predicting secondary structures with thermodynamic methods is still not feasible when the RNA molecules have long nucleotide sequences and include complex motifs such as pseudoknots. This paper presents RNAVLab (RNA Virtual Laboratory), a virtual laboratory for studying RNA secondary structures including pseudoknots that allows scientists to address this challenge. Two important case studies show the versatility and functionalities of RNAVLab. The first study quantifies its capability to rebuild longer secondary structures from motifs found in systematically sampled nucleotide segments. The extensive sampling and predictions are made feasible in a short turnaround time because of the grid technology used. The second study shows how RNAVLab allows scientists to study the viral RNA genome replication mechanisms used by members of the virus family Nodaviridae.


title: Could individuals from countries using bcg vaccination be resistant to sars-cov-2 induced infections?/ Verem aşısı uygulayan ülkelerin bireyleri sars-cov-2 virüsünün yol açtığı enfeksiyona karşı daha dirençli olabilir mi?

text: The lower than expected number of SARS-CoV-2 cases in countries with fragile health systems is puzzling. Herein, we hypothesize that BCG vaccination policies and vaccine strain preferences adopted by different countries might influence the SARS-CoV-2 transmission patterns and/or COVID-19 associated morbidity and mortality. We also postulate that until a specific vaccine is developed, SARS-CoV-2 vulnerable populations could be immunized with BCG vaccines to attain heterologous nonspecific protection from the new coronavirus. In the lights of our investigations the most resistant countries appear to be the ones using Group I BCG strain. Within these countries, however, those who employs Russian strain is even more protected against COVID-19 infection.


title: Necessity and feasibility of viral RNA detection in specialist ophthalmic institute during the COVID-19 epidemic/ 新型冠状病毒肺炎防控期间眼专科机构开展病毒核酸检测的必要性和可行性评估

text: The prevention and treatment of COVID-19 in China is now at a key stage.The tasks faced by the medical organs are fighting against the COVID-19 while providing the medical services orderly.As a Specialist medical institution nationwide, ophthalmic hospitals are resuming receiving patients and performing operations gradually, including precision interruption of the epidemic, prevention of the secondary virus transmission, and avoidance of nosocomial cross infection among health care providers are required.We explored a multifaceted management for the prevention and control of epidemic, with a special focus on the individual protection for patients and medical staffs.A preliminary positive effect can be observed as a result.The main measures taken cover two aspects.On the one hand, 2019-nCoV ribonucleic acid (RNA) detection and hematological indices inspection including C-reactive protein (CRP) and serum amyloid A (SAA) are listed as routine tests of preoperative screening for ocular surgical patients.These tests are required to be completed upon the admission to avoid the possibility of accepting any asymptomatic infected individual and to reduce the risk of nosocomial cross infection.On the other hand, the 2019-nCoV RNA detection is also provided to high-risk employees who visited affected area recently.This assists in obtaining guarantee in both safety and quality of medical services provided, but also helps in lessening the mental and spiritual stress for medical staffs.It is expected that these measures can contribute to the work of our peers of ophthalmology in the prevention and control of COVID-19 and to the safe environment where the medical services are provided, and provide a reference for other outbreak of virus-causing disease.


title: Elevated RDW is Associated with Increased Mortality Risk in COVID-19

text: Abstract Background Coronavirus disease 2019 (COVID19) is an acute respiratory illness with a high rate of hospitalization and mortality. Prognostic biomarkers are urgently needed. Red blood cell distribution width (RDW), a component of complete blood counts that reflects cellular volume variation, has been shown to be associated with elevated risk for morbidity and mortality in a wide range of diseases. Methods We retrospectively studied the relationship between RDW and COVID19 mortality risk for 1198 adult patients diagnosed with SARS COV2 at 4 Partners Healthcare Network Hospitals between March 4, 2020, and April 28, 2020. Findings Elevated RDW (> 14.5%) was associated with increased mortality in patients of all ages with a risk ratio of 2.5 (95% CI, 2.3-2.8). Stratified by age, the risk ratio was 6.2 (4.4-7.9, N = 312) < 50 years, 3.2 (2.5-4.1, N = 230) 50-60, 2.3 (1.6-3.1, N = 236) 60-70, 1.2 (0.7-1.8, N = 203) 70-80, and 1.9 (1.5-2.3, N = 216) > 80 years. RDW was significantly associated with mortality in Cox proportional hazards models adjusted for age, D-Dimer, absolute lymphocyte count, and common comorbidities (p < 1e-4 for RDW in all cases). Patients whose RDW increased during admission had a ~3-fold elevation in mortality risk compared to those whose RDW did not change. Interpretation Elevated RDW at diagnosis and an increase in RDW during admission are both associated with increased mortality risk for adult COVID19 patients at a large academic medical center network.


title: Coronavirus Disease 2019 (COVID-19): An Evidence Map of Medical Literature

text: Since the beginning of the COVID-19 outbreak in December 2019, a substantial body of COVID-19 medical literature has been generated. As of May 2020, gaps in the existing literature remain unidentified and, hence, unaddressed. In this paper, we summarise the medical literature on COVID-19 between 1 January and 24 March 2020 using evidence maps and bibliometric analysis in order to systematically identify gaps and propose areas for valuable future research. The examined COVID-19 medical literature originated primarily from Asia and focussed mainly on clinical features and diagnosis of the disease. Many areas of potential research remain underexplored, such as mental health research, the use of novel technologies and artificial intelligence, research on the pathophysiology of COVID-19 within different body systems, and research on indirect effects of COVID-19 on the care of non-COVID-19 patients. Research collaboration at the international level was limited although improvements may aid global containment efforts.


title: Intensive Care Unit Resource Planning During COVID-19 Emergency at the Regional Level: the Italian case.

text: Severe acute respiratory syndrome Covid-19 (SARS-CoV-2) has been declared a worldwide emergency and a pandemic disease by the World Health Organisation (WHO). It started in China in December 2019, and it is currently rapidly spreading throughout Italy, which is now the most affected country after China. There is great attention for the diffusion and evolution of the CoVid-19 infection which started from the north (particularly in the Lombardia region) and it is now rapidly affecting other Italian regions. We investigate on the impact of patients hospitalisation in Intensive Care Units (ICUs) at a regional and subregional granularity. We propose a model derived from well-known models in epidemic to estimate the needed number of places in intensive care units. The model will help decision-makers to plan resources in the short and medium-term in order to guarantee appropriate treatments to all patients needing it. We analyse Italian data at regional level up to March 15th aiming to: (i) support health and government decision-makers in gathering rapid and efficient decisions on increasing health structures capacities (in terms of ICU slots) and (ii) define a scalable geographic model to plan emergency and future CoVid-19 patients management using reallocating them among health structures. Finally, the here proposed model can be useful in countries where CoVid-19 is not yet strongly diffused.


title: Genome-wide CRISPR screen reveals host genes that regulate SARS-CoV-2 infection

text: Identification of host genes essential for SARS-CoV-2 infection may reveal novel therapeutic targets and inform our understanding of COVID-19 pathogenesis. Here we performed a genome-wide CRISPR screen with SARS-CoV-2 and identified known SARS-CoV-2 host factors including the receptor ACE2 and protease Cathepsin L. We additionally discovered novel pro-viral genes and pathways including the SWI/SNF chromatin remodeling complex and key components of the TGF-β signaling pathway. Small molecule inhibitors of these pathways prevented SARS-CoV-2-induced cell death. We also revealed that the alarmin HMGB1 is critical for SARS-CoV-2 replication. In contrast, loss of the histone H3.3 chaperone complex sensitized cells to virus-induced death. Together this study reveals potential therapeutic targets for SARS-CoV-2 and highlights host genes that may regulate COVID-19 pathogenesis.


title: How fast does the SARS-Cov-2 virus really mutate in heterogeneous populations?

text: We introduce the problem of determining the mutational support of genes in the SARS-Cov-2 virus and estimating the distribution of mutations within different genes using small sample sizes that do not allow for accurate maximum likelihood estimation. The mutational support refers to the unknown number of sites mutated across all strains and individual samples of the SARS-Cov-2 genome; given the high cost and limited availability of real-time polymerase chain reaction (RT-PCR) test kits, especially in early stages of infections when only a small number of genomic samples (∼ 1000s) are available that do not allow for determining the exact degree of mutations in an RNA virus that comprises roughly 30, 000 nucleotides. Nevertheless, working with small sample sets is required in order to quickly predict the mutation rate of this and other viruses and get an insight into their transformational power. Furthermore, with the small number of samples available, it is hard to estimate the mutational landscape across different age/gender groups and geographical locations which may be of great importance in assessing different risk categories and factors influencing susceptibility to infection. To this end, we use our state-of-the art polynomial estimator techniques and the Good-Turing estimator to obtain estimates based on only roughly 1, 000 samples per category. Our analysis reveals an interesting finding: the mutational support appears to be statistically more significant in patients which appear to have lower infection rates and handle the exposure with milder symptoms, such as women and people of relatively young age (≤ 55).


title: Genomic epidemiology of SARS-CoV-2 spread in Scotland highlights the role of European travel in COVID-19 emergence

text: Abstract SARS-CoV-2, the causative agent of COVID-19, emerged in Wuhan, China in December 2019 and spread rapidly throughout the world. Understanding the introductions of this new coronavirus in different settings may assist control efforts and the establishment of frameworks to support rapid response in future infectious disease outbreaks. We investigated the first four weeks of emergence of the SARS-CoV-2 virus in Scotland after the first case reported on the 1st March 2020. We obtained full genome sequences from 452 individuals with a laboratory-confirmed diagnosis of COVID-19, representing 20% of all cases until 1st April 2020 (n=2310). This permitted a genomic epidemiology approach to study the introductions and spread of the SARS-2 virus in Scotland. From combined phylogenetic and epidemiological analysis, we estimated at least 113 introductions of SARS-CoV-2 into Scotland during this period. Clusters containing multiple sequences suggestive of onward transmission occurred in 48/86 (56%). 42/86 (51%) clusters had no known international travel history indicating undetected introductions. The majority of viral sequences were most closely related to those circulating in other European countries, including Italy, Austria and Spain. Travel-associated introductions of SARS-CoV-2 into Scotland predated travel restrictions in the UK and other European countries. The first local transmission occurred three days after the first case. A shift from travel-associated to sustained community transmission was apparent after only 11 days. Undetected introductions occurred prior to the first known case of COVID-19. Earlier travel restrictions and quarantine measures might have resulted in fewer introductions into Scotland, thereby reducing the number of cases and the subsequent burden on health services. The high number of introductions and transmission rates were likely to have impacted on national contact tracing efforts. Our results also demonstrate that local real-time genomic epidemiology can be used to monitor transmission clusters and facilitate control efforts to restrict the spread of COVID-19.


title: Chest Computed Tomography Findings in Asymptomatic Patients with COVID-19

text: Background: Little is known about the damage to the respiratory system in asymptomatic patients with coronavirus disease (COVID-19). Objective: Herein, we evaluated the findings of chest computed tomography (CT) and radiography in patients with COVID-19 who were asymptomatic. Methods: We retrospectively investigated patients with a confirmed diagnosis of COVID-19 but who did not show any symptoms. Among the 139 patients with COVID-19 who were hospitalized, 10 (7.2%) were asymptomatic. Their chest CT and radiographic findings were analyzed. Results: In the results, all patients (100%) had ground glass opacity (GGO) on chest CT. Further, the GGO lesions were predominantly distributed peripherally and posteriorly in all patients. In 9 (90%) patients, the GGO lesions were combined with reticular opacity. Air-bronchogram due to bronchiolectasis surrounded by GGO was observed in 8 patients (80%). Additionally, the lung lesions were dominant on the right side in all patients. Conclusions: In conclusion, considering our results that the lung is affected in asymptomatic patients, it will be necessary to extend the indications of COVID-19 testing for effective management of COVID-19 during the pandemic.


title: Proteome-wide analysis of differentially-expressed SARS-CoV-2 antibodies in early COVID-19 infection

text: Rapid and accurate tests that detect IgM and IgG antibodies to SARS-CoV-2 proteins are essential in slowing the spread of COVID-19 by identifying patients who are infected with COVID-19. Using a SARS-CoV-2 proteome microarray developed in our lab, we comprehensively profiled both IgM and IgG antibodies in forty patients with early-stage COVID-19, influenza, or non-influenza who had similar symptoms. The results revealed that the SARS-CoV-2 N protein is not an ideal biomarker for COVID-19 diagnosis because of its low immunogenicity, thus tests that rely on this marker alone will have a high false negative rate. Our data further suggest that the S protein subunit 1 receptor binding domain (S1-RBD) might be the optimal antigen for IgM antibody detection, while the S protein extracellular domain (S1+S2ECD) would be the optimal antigen for both IgM and IgG antibody detection. Notably, the combination of all IgM and IgG biomarkers can identify 87% and 73.3% COVID-19 patients, respectively. Finally, the COVID-19-specific antibodies are significantly correlated with the clinical indices of viral infection and acute myocardial injury (p≤0.05). Our data may help understand the function of anti-SARS-CoV-2 antibodies and improve serology tests for rapid COVID-19 screening.


title: Estimating the proportion of coronavirus disease 2019 (COVID-19) cases among households in France : a cross-sectional study on individuals with myocardial infarction history

text: Background: Previous studies have identified that adults with cardiovascular diseases were disproportionately associated with a significantly increased risk of a severe form of COVID-19 and all-cause mortality. We aimed to describe the diagnosed COVID-19 cases and to estimate the symptomatic and asymptomatic suspected cases among individuals with pre-existing myocardial infarction myocardial infarction and their relatives in lockdown period. Methods: We conducted a two-week cross-sectional telephone survey, from May 4 to May 15, 2020, including all households with at least one individual with pre-existing cardiovascular disease in the past two years. We defined a suspected COVID-19 case when living with at least one individual tested positive to COVID-19, or when an individual has been in contact with a suspected or confirmed case since the March 1rst, or when a relative from the same house has been hospitalized or deceased for COVID-19. Results: We observed high rates of compliance with health measures during the lockdown period, regardless of age or risk factors. Among individuals with myocardial infarction history, two were COVID-19 confirmed, 13.37% were suspected (94/703) of whom 70.21% (66/94) asymptomatic. Conclusions: Individuals with myocardial infarction history presented different symptoms association with more respiratory signs. This population, which is older and associated with more comorbidities, is exposed to a high risk of complication in the event of contamination. Infection rates are relevant to adjusting the management of emergency departments in our region.


title: Is the fit of N95 facial masks effected by disinfection? A study of heat and UV disinfection methods using the OSHA protocol fit test.

text: The current COVID-19 pandemic has highlighted global supply chain shortcomings in the US hospital delivery system, most notably personal protective equipment (PPE) and COVID-19 is found on these masks ~ 7 days. Recent work from our group has shown two promising disinfection methods for N95 facial masks, dry heat (hot air (75C, 30 min) and UVGI which is UVGI 254 nm, 8W, 30 min. Using N95 five models of N95 masks from three different manufacturers we determined the following: 1) Hot air treated N95 masks applied over 5 cycles did not degrade the fit of masks (1.5% change in fit factor, p = .67), 2) UVGI treated N95 masks applied over 10 cycles were significantly degraded in fit and did not pass quantitative fit testing using OSHA testing protocols on a human model (-77.4% change in fit factor, p = .0002).


title: SARS-CoV-2 seroprevalence in the municipality of Sao Paulo, Brazil, ten weeks after the first reported case

text: A population-based household survey was performed to estimate the prevalence of IgM and IgG to SARS-CoV-2 in residents of six districts in Sao Paulo City, Brazil. Serum samples collected from 299 randomly-selected adults and 218 cohabitants (N=517) were tested by chemiluminescence immunoassay ten weeks after the first reported case. Weighted overall seroprevalence was 4.7% (95% CI 3.0-6.6%). The low seroprevalence suggests that most of this population could still be infected. Serial serosurveys were initiated aiming to monitor the progress of the ongoing pandemic throughout the entire city. This may help inform public health authority decisions regarding prevention and control strategies.


title: Recovery Ratios Reliably Anticipate COVID-19 Pandemic Progression

text: The COVID-19 pandemic is placing unprecedented demands on healthcare systems worldwide and exacting a massive humanitarian toll. This makes the development of accurate predictive models imperative, not just for understanding the course of the pandemic but more importantly for gaining insight into the efficacy of public health measures and planning accordingly. Epidemiological models are forced to make assumptions about many unknowns and therefore can be unreliable. Here, taking an empirical approach, we report a 20-30 day lag between the peak of confirmed to recovered cases and the peak of daily deaths in each country, independent of the epoch of that country in its pandemic cycle. This analysis is expected to be largely independent of the proportion of the population being tested and therefore should aid in planning around the timing and easing of public health measures. Our data also suggests broad predictions for the number of fatalities, generally somewhat lower than most other models. Finally, our model suggests that the world as a whole is shortly to enter a recovery phase, at least as far as the first pandemic wave is concerned.


Roles of the clinical pharmacist during the COVID-19 pandemic


title: Initial public health response and interim clinical guidance for the 2019 novel coronavirus outbreak — United States, December 31, 2019–February 4, 2020

text: This article summarizes what is currently known about the 2019 novel coronavirus and offers interim guidance.


title: RT-PCR testing to detect a COVID-19 outbreak in Austria: rapid, accurate and early diagnosis in primary care (The REAP study)

text: Background Delay in COVID-19 detection has led to a major pandemic. We report rapid early detection of SARS-CoV-2 by reverse transcriptase-polymerase chain reaction (RT-PCR), comparing it to the serostatus of convalescent infection, at an Austrian National Sentinel Surveillance Practice in an isolated ski-resort serving a population of 22,829 people. Methods Retrospective dataset of all 73 patients presenting with mild to moderate flu-like symptoms to a sentinel practice in the ski-resort of Schladming-Dachstein, Austria, between 24 February and 03 April, 2020. We split the outbreak in two halves, by dividing the period from the first to the last case by two, to characterise the following three cohorts of patients with confirmed infection: people with reactive RT-PCR presenting during the first half (early acute infection) vs. those presenting in the second half (late acute), and people with non-reactive RT-PCR (late convalescent). For each cohort we report the number of cases detected, the accuracy of RT-PCR and the duration of symptoms. We also report multivariate regression of 15 clinical symptoms as covariates, comparing all people with convalescent infection to those with acute infection. Findings All 73 patients had SARS-CoV-2 RT-PCR testing. 22 patients were diagnosed with COVID-19, comprising: 8 patients presenting early acute, and 7 presenting late acute and 7 late convalescent respectively; 44 patients tested SARS-COV-2 negative, and 7 were excluded. RT-PCR sensitivity was high (100%) among acute presenters, but dropped to 50% in the second half of the outbreak; specificity was 100%. The mean duration of symptoms was 2 days (range 1-4) among early acute presenters, and 4.4 days (1-7) among late acute and 8 days (2-12) among late convalescent presenters respectively. Convalescent infection was only associated with loss of taste (ORs=6.02;p=0.047). Acute infection was associated with loss of taste (OR=571.72;p=0.029), nausea and vomiting (OR=370.11;p=0.018), breathlessness (OR=134.46;p=0.049), and myalgia (OR=121.82;p=0.032); but not loss of smell, fever or cough. Interpretation RT-PCR rapidly and reliably detects early COVID-19 among people presenting with viral illness and multiple symptoms in primary care, particularly during the early phase of an outbreak. RT-PCR testing in primary care should be prioritised for effective COVID-19 prevention and control.


title: On the COVID-19 Pandemic in Indian State of Maharashtra: Forecasting & Effect of different parameters

text: This work details the outbreak and factors affecting the spread of novel coronavirus (COVID-19) in the Indian state of Maharashtra, which is considered as one of the most massive and deadly pandemic outbreaks. Observational data collected between 14 March 2020 and 4 May 2020 is statistically analyzed to determine the nonlinear behaviour of the epidemic. It is followed by validating predicted results with real-time data. Proposed model is further used to obtain statistical summaries in which Grubbs tests for outlier detection have justified high values of evaluation metrics. Outliers are found to be pilot elements in an outbreak under considered region. Statistically, a significant correlation has been observed between dependent and explanatory variables. Transmission pattern of this virus is very much different from the SARS-CoV-1 virus. Key findings of this work will be predominant in maintaining environment conditions at healthcare facilities to reduce transmission rates at these most vulnerable places. KEY WORDS-: SARS-CoV-1; COVID-19, Humidity, Polynomial, Temperature, Confirmed cases; Tests; Maharashtra.


title: High Throughput Designing and Mutational Mapping of RBD-ACE2 Interface Guide Non-Conventional Therapeutic Strategies for COVID-19

text: Considering the current status of the SARS-CoV-2 pandemic, sequence variations and possibly structural changes in the rapidly evolving SARS-CoV-2 is highly expected in the coming months. The SARS-CoV-2 spike (S) protein is responsible for mediating viral attachment and fusion with cell membranes. Mutations in the receptor-binding domain (RBD) of the S-protein occur at the most variable part of the SARS-CoV-2 genome, and specific sites of S-protein have undergone positive selection impacting the viral pathogenicity. In the present work, we used high-throughput computation to design 100,000 mutants in RBD interfacial residues and identify novel affinity-enhancing and affinity-weakening mutations. Our data suggest that SARS-CoV-2 can establish a higher rate of infectivity and pathogenesis when it acquires combinatorial mutations at the interfacial residues in RBD. Mapping of the mutational landscape of the interaction site suggests that a few of these residues are the hot-spot residues with a very high tendency to undergo positive selection. Knowledge of the affinity-enhancing mutations may guide the identification of potential cold-spots for this mutation as targets for developing a possible therapeutic strategy instead of hot-spots, and vice versa. Understanding of the molecular interactions between the virus and host protein presents a detailed systems view of viral infection mechanisms. The applications of the present research can be explored in multiple antiviral strategies, including monoclonal antibody therapy, vaccine design, and importantly in understanding the clinical pathogenesis of the virus itself. Our work presents research directions for the exploitation of non-conventional solutions for COVID-19.


title: #lockdown: Network-Enhanced Emotional Profiling in the Time of COVID-19

text: The COVID-19 pandemic forced countries all over the world to take unprecedented measures, like nationwide lockdowns To adequately understand the emotional and social repercussions, a large-scale reconstruction of how people perceived these unexpected events is necessary but currently missing We address this gap through social media by introducing MERCURIAL (Multi-layer Co-occurrence Networks for Emotional Profiling), a framework which exploits linguistic networks of words and hashtags to reconstruct social discourse describing real-world events We use MERCURIAL to analyse 101,767 tweets from Italy, the first country to react to the COVID-19 threat with a nationwide lockdown The data were collected between the 11th and 17th March, immediately after the announcement of the Italian lockdown and the WHO declaring COVID-19 a pandemic Our analysis provides unique insights into the psychological burden of this crisis, focussing on—(i) the Italian official campaign for self-quarantine (#iorestoacasa), (ii) national lockdown (#italylockdown), and (iii) social denounce (#sciacalli) Our exploration unveils the emergence of complex emotional profiles, where anger and fear (towards political debates and socio-economic repercussions) coexisted with trust, solidarity, and hope (related to the institutions and local communities) We discuss our findings in relation to mental well-being issues and coping mechanisms, like instigation to violence, grieving, and solidarity We argue that our framework represents an innovative thermometer of emotional status, a powerful tool for policy makers to quickly gauge feelings in massive audiences and devise appropriate responses based on cognitive data