title: Study of Air Curtain in Context of Individual Protection from Exposure to Coronavirus (SARS-CoV-2) Contained in Cough-Generated Fluid Particles

text: The ongoing respiratory COVID-19 pandemic has heavily impacted the social and private lives of the majority of the global population. This infection is primarily transmitted via virus-laden fluid particles (i.e., droplets and aerosols) that are formed in the respiratory tract of infected individuals and expelled from the mouth in the course of breathing, talking, coughing, and sneezing. To mitigate the risk of virus transmission, in many places of the world, the public has been asked or even obliged to use face covers. It is plausible that in the years ahead we will see the use of face masks, face shields and respirators become a normal practice in our life. However, wearing face covers is uncomfortable in some situations, like, for example, in summer heat, while staying on beaches or at hotel swimming pools, doing exercises in gyms, etc. Also, most types of face cover become contaminated with time and need to be periodically replaced or disinfected. These nuisances are caused by the fact that face covers are based on material barriers, which prevent inward and outward propagation of aerosol and droplets containing the pathogen. Applying well established gas-particle flow formalism, we study a non-material based protection barrier created by a flow of well directed down stream of air across the front of the open face. The~protection is driven by dragging virus-laden particles inside the width of the air flow and hence, as a consequence, displacing them away from their primary trajectories. The study, shows that such, potentially portable, air curtains can effectively provide both inward and outward protection and serve as an effective personal protective equipment (PPE) mitigating human to human transmission of virus infection like COVID-19.


title: Multi-level proteomics reveals host-perturbation strategies of SARS-CoV-2 and SARS-CoV

text: The sudden global emergence of SARS-CoV-2 urgently requires an in-depth understanding of molecular functions of viral proteins and their interactions with the host proteome. Several omics studies have extended our knowledge of COVID-19 pathophysiology, including some focused on proteomic aspects1–3. To understand how SARS-CoV-2 and related coronaviruses manipulate the host we here characterized interactome, proteome and signaling processes in a systems-wide manner. This identified connections between the corresponding cellular events, revealed functional effects of the individual viral proteins and put these findings into the context of host signaling pathways. We investigated the closely related SARS-CoV-2 and SARS-CoV viruses as well as the influence of SARS-CoV-2 on transcriptome, proteome, ubiquitinome and phosphoproteome of a lung-derived human cell line. Projecting these data onto the global network of cellular interactions revealed relationships between the perturbations taking place upon SARS-CoV-2 infection at different layers and identified unique and common molecular mechanisms of SARS coronaviruses. The results highlight the functionality of individual proteins as well as vulnerability hotspots of SARS-CoV-2, which we targeted with clinically approved drugs. We exemplify this by identification of kinase inhibitors as well as MMPase inhibitors with significant antiviral effects against SARS-CoV-2.


title: Knowledge, Attitude, Perceptions and Practice towards COVID-19: A systematic review and Meta-analysis

text: Background: Several studies among various population groups have been conducted to investigate the level of knowledge, attitudes, perceptions, and risk reduction practices (KAP) related to COVID-19. A comprehensive review on this topic is important to highlight the areas for improvement and interventions to prevent COVID-19. Thus, the purpose of this study was to summarize the level of KAP about COVID-19 via a systematic review Methods: A systematic literature search was performed using a combination of selected keywords in four scientific databases to identify relevant literature published from January 1 to May 31, 2020. Nineteen articles were included in the systematic review, and sixteen studies in the meta-analysis. The data was analyzed using a random-effects model due to the heterogeneity between the studies. Results: Lack of COVID-19-related knowledge, positive perceptions, and preventive practices was detected and seems widespread. In particular, 56.6% (95%CI: 45.9-67%) of the health care workers (HCWs) and medical students had poor knowledge about COVID-19 and only 46% (95%CI: 15-77) of the total study sample had positive perceptions towards COVID-19. Besides, 81.7% of the sample prioritized practicing hand hygiene to prevent COVID-19, but wearing a face mask to prevent COVID-19 transmission was suboptimal (73.4%). Finally, less than a tenth (8%) of the subjects had good knowledge about COVID-19 symptoms (79%) and its transmission (82%) and reported that they avoided crowded places to prevent getting COVID-19 (89%). Conclusion: Evidence-based practices on risk communication and raising awareness should be planned by local governments in collaboration with healthcare organizations. Specifically, educational initiatives for HCWs to prioritize wearing a face mask and practicing hand hygiene should be considered a priority.


title: Invisible Crowns : Public Communication on the Novel Coronavirus in Norway

text: At the beginning of April, the Norwegian government announced that the coronavirus outbreak is to be under control and social functions will be gradually resumed The governmental structure for crisis preparedness and management is fragmented but some administrative coordinating and support functions work well in Norway Norwegian Institute of Public Health (NIPH) currently provides readable advice and information about the novel coronavirus disease, including a systematic map on the disease evidence and rapid reviews of latest academic articles Norwegian authorities maintain a high degree of public trust though they have failed to perform effective public communication at times Citizens seem to make a cool-headed decision based on experts’ intellectual humility and personal emotion in their delivery of information The cool-headedness would be a key to face and keep the new normal ‘strangeness’ in the midst of and after the coronavirus crisis


title: Basic reproduction number of 2019 Novel Coronavirus Disease in Major Endemic Areas of China: A latent profile analysis

text: Objective: The aim of the study is to analyze the latent class of basic reproduction number (R0) trend of 2019 novel coronavirus disease (COVID−19) in major endemic areas of China. Methods The provinces that reported more than 500 cases of COVID−19 till February 18, 2020 were selected as the major endemic area. The Verhulst model was used to fit the growth rate of cumulative confirmed cases. The R0 of COVID−19 was calculated using the parameters of severe acute respiratory syndrome (SARS) and COVID−19, respectively. The latent class of R0 was analyzed using a latent profile analysis model. Results The median R0 calculated from SARS and COVID−19 parameters were 1.84 − 3.18 and 1.74 − 2.91, respectively. The R0 calculated from the SARS parameters was greater than that of calculated from the COVID−19 parameters (Z = −4.782 − −4.623, P < 0.01). Both R0 can be divided into three latent classes. The initial value of R0 in class 1 (Shandong Province, Sichuan Province and Chongqing Municipality) was relatively low and decreases slowly. The initial value of R0 in class 2 (Anhui Province, Hunan Province, Jiangxi Province, Henan Province, Zhejiang Province, Guangdong Province and Jiangsu Province) was relatively high and decreases rapidly. Moreover, the initial value of R0 of class 3 (Hubei Province) was between that of class 1 and class 2, but the higher level of R0 lasts longer and decreases slowly. Conclusion The results indicated that overall trend of R0 has been falling with the strengthening of China's comprehensive prevention and control measures for COVID−19, however, presents regional differences.


title: CoV Genome Tracker: tracing genomic footprints of Covid-19 pandemic

text: Summary Genome sequences constitute the primary evidence on the origin and spread of the 2019-2020 Covid-19 pandemic. Rapid comparative analysis of coronavirus SARS-CoV-2 genomes is critical for disease control, outbreak forecasting, and developing clinical interventions. CoV Genome Tracker is a web portal dedicated to trace Covid-19 outbreaks in real time using a haplotype network, an accurate and scalable representation of genomic changes in a rapidly evolving population. We resolve the direction of mutations by using a bat-associated genome as outgroup. At a broader evolutionary time scale, a companion browser provides gene-by-gene and codon-by-codon evolutionary rates to facilitate the search for molecular targets of clinical interventions. Availability and Implementation CoV Genome Tracker is publicly available at http://cov.genometracker.org and updated weekly with the data downloaded from GISAID (http://gisaid.org). The website is implemented with a custom JavaScript script based on jQuery (https://jquery.com) and D3-force (https://github.com/d3/d3-force). Contact weigang@genectr.hunter.cuny.edu, City University of New York, Hunter College Supplementary Information All supporting scripts developed in JavaScript, Python, BASH, and PERL programming languages are available as Open Source at the GitHub repository https://github.com/weigangq/cov-browser.


title: Ostavimir is ineffective against COVID-19: in silico assessment, in vitro and retrospective study

text: As a neuraminidase inhibitor, oseltamivir has effectively combated the pandemic influenza A and B, so it is a first-line commonly used antiviral drug, especially in primary hospitals. At the same time, oseltamivir, as an over-the-counter drug, is also a popular antiviral drug. As healthcare workers fighting against coronavirus disease 2019 (COVID-19), we have found that many patients experiencing discomfort or considered to be infected with a virus take oseltamivir. From severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 to middle east respiratory syndrome coronavirus (MERS-CoV) in 2012, and now the current COVID-19 epidemic, there is not plenty of evidence showing that oseltamivir is effective against coronavirus. Still, there is also no sufficient evidence to refute its ineffectiveness. We cannot predict whether there will be a pandemic of respiratory coronavirus in the future, so we hope to initiate such research and preliminarily explore whether oseltamivir is effective for COVID-19, which can better guide healthcare workers in the selection of appropriate antiviral drugs in the face of coronavirus epidemics. If oseltamivir is effective, then a wide promotion of its application often can achieve a double effect with half the effort. If it is not effective, then considering the side effects of oseltamivir, it is not necessary to use unreasonable drugs that will not slow the progression of the disease but can cause adverse reactions. We found that oseltamivir is not suitable for fighting against COVID-19 through the method of computer aided drug design and in vitro study and retrospective case study. Meanwhile it was high-occurrence seasons for the influenza, COVID-19 should be highly suspected in patients who did not benefit from oseltamivir. We hope that the result of our study could be shared with the frontline physicians in fighting against COVID-19.


title: Impact of COVID-19 infection on maternal and neonatal outcomes: a review of 287 pregnancies

text: Pregnant women are vulnerable group in viral outbreaks especially in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The aim of this review was to identify maternal and neonatal outcomes in available articles on pregnancies affected by COVID-19. The articles that had assessed outcomes of pregnancy and perinatal of women with COVID-19 between Oct 2019 and Apr 30, 2020 without language limitation were considered. All kinds of studies such as case report, case series, retrospective cohort, case control were included. We searched databases, selected relevant studies and extracted data regarding maternal and neonatal outcomes from each article. Data of 287 pregnant women with COVID-19 of 6 countries were assessed from 28 articles between December 8, 2019 and April 6, 2020. Most pregnant women reported in their third trimester, 102 (35.5%) cases were symptomatic at the time of admission. Common onset symptoms, abnormal laboratory findings, and chest computed tomography pattern were fever (51.5%), lymphocytopenia (67.9%), and multiple ground-glass opacities (78.5%) respectively. 93% of all deliveries were done through cesarean section. No maternal mortality and 3 % ICU admission were reported. Vertical transmission was not reported but its possibility was suggested in three neonates. One neonatal death, one stillbirth, and one abortion were reported. All newborns were not breastfed. This review showed fewer adverse maternal and neonatal outcomes in pregnant women with COVID-19 in comparison with previous coronavirus outbreak infection in pregnancy. Limited data are available regarding possibility of virus transmission in utero, during vaginal childbirth and breastfeeding. Effect of COVID-19 on first and second trimester and ongoing pregnancy outcomes in infected mothers is still questionable.


title: A Novel Three-Layer IoT Architecture for Shared, Private, Scalable, and Real-time Machine Learning from Ubiquitous Cyber-Physical Systems

text: Abstract Due to the recent movements in Industry 4.0 and Internet of Things (IoT), accessing or generating data in the Smart Manufacturing (SM) domain has become more attainable; communication protocols such as MTConnect and OPC-UA provide access to a majority of raw data generated from machine tools while retrofit sensor packs facilitate high-frequency data acquisitions from legacy and modern equipment. These technologies have led to the generation of quantities of raw data, known as Big Data (BD), that are complex to be analyzed. This study proposes a novel and event-driven IoT architecture that considers automated and scalable machine learning techniques with the focus sense-making from manufacturing process and systems performance in the Cyber-Physical Systems (CPS) domain. In this manuscript, a novel generalized three-layer IoT architecture utilizing Edge Computing (EC), Fog Computing (FC), Cloud Computing (CC), and Federated Learning (FL) is presented, where data are preprocessed in the Edge layer, Machine Learning (ML) models are incrementally trained in the Fog layer and the trained models are aggregated in centralized cloud models. The results show that the methods discussed in the proposed architecture will lead to the development of higher performance and more scalable IoT frameworks that require minimal storage and computing power.


title: Letter to the Editor: Note on published research on the effects of COVID-19 on the environment without sufficient depth of science

text: Dear Editor-in-Chief: We have given two articles published recently in Science of the Total Environment by Mandal and Pal (2020) and Zambrano-Monserrate et al. (2020) a thorough reading. Both articles present a significant association between the novel Coronavirus (COVID-19) social distancing policies and improvement in environmental quality such as air pollution, land surface temperature, and noise. Both articles present good research, complemented by detailed explanations and displays, yet we have a few concerns that affect the interpretation and meaning of the results.


title: Critical Questions when Interpreting Coronavirus PCR Diagnostics

text: The results of PCR measurements are regarded as unquestionable. This statement must be put into perspective. This relativization is particularly important in connection with the interpretation of SARS-CoV-2 results. Members of the critical infrastructure, such as nurses, may be quarantined although this is not necessary and are therefore missing from patient care. With our small but impressive comparison of methods and transport media for SARS-CoV-2, we not only show the different sensitivity of common routine systems and media in laboratory medicine. Further, we would like to inform clinically working physicians, who are not familiar with the technical weaknesses of the PCR investigation, about gaps and present solutions for their daily work.


title: Deposition distribution of the new coronavirus (SARS-CoV-2) in the human airways upon exposure to cough-generated aerosol

text: The new coronavirus disease 2019 (COVID-19) has been emerged as a rapidly spreading pandemic. The disease is thought to spread mainly from person-to-person through respiratory droplets produced when an infected person coughs, sneezes, or talks. The pathogen of COVID-19 is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It infects the cells binding to the angiotensin-converting enzyme 2 receptor (ACE2) which is expressed by cells throughout the airways as targets for cellular entry. Although the majority of persons infected with SARS-CoV-2 experience symptoms of mild upper respiratory tract infection, in some people infections of the peripheral airways result in severe, potentially fatal pneumonia. However, the induction of COVID-19 pneumonia requires that SARS-CoV-2 reaches the peripheral airways. While huge efforts have been made to understand the spread of the disease as well as the pathogenesis following cellular entry, much less attention is paid how SARS-CoV-2 from the environment reach the receptors of the target cells. The aim of the present study is to characterize the deposition distribution of SARS-CoV-2 in the airways upon exposure to cough-generated aerosol. For this purpose, the Stochastic Lung Deposition Model has been applied. Aerosol size distribution and breathing parameters were taken from the literature supposing normal breathing through the nose. We found that the probability of direct infection of the peripheral airways due to inhalation of aerosol generated by a bystander cough is very low. As the number of pathogens deposited in the extrathoracic airways is ~10 times higher than in the peripheral airways, we concluded that in most cases COVID-19 pneumonia must be preceded by SARS-CoV-2 infection of the upper airways. Our results suggest that without the enhancement of viral load in the upper airways, COVID-19 would be much less dangerous. The period between the onset of initial symptoms and the potential clinical deterioration could provide an opportunity for prevention of pneumonia by blocking or significantly reducing the transport of viruses towards the peripheral airways. Coughing into a tissue or cloth even at home in order to absorb the emitted aerosol is highly recommended to avoid the continuous re-inhalation of own cough.


title: Appendix A Biosafety in the virology laboratory

text: Unknown


title: Toilets dominate environmental detection of SARS-CoV-2 virus in a hospital

text: Background: Respiratory and faecal aerosols play a suspected role in transmitting the SARS-CoV-2 virus. We performed extensive environmental sampling in a dedicated hospital building for Covid-19 patients in both toilet and non-toilet environments, and analysed the associated environmental factors. Methods: We collected data of the Covid-19 patients. 107 surface samples, 46 air samples, two exhaled condensate samples, and two expired air samples were collected were collected within and beyond the four three-bed isolation rooms. We reviewed the environmental design of the building and the cleaning routines. We conducted field measurement of airflow and CO2 concentrations. Findings: The 107 surface samples comprised 37 from toilets, 34 from other surfaces in isolation rooms (ventilated at 30-60 L/s), and 36 from other surfaces outside isolation rooms in the hospital. Four of these samples were positive, namely two ward door-handles, one bathroom toilet-seat cover and one bathroom door-handle; and three were weakly positive, namely one bathroom toilet seat, one bathroom washbasin tap lever and one bathroom ceiling-exhaust louvre. One of the 46 air samples was weakly positive, and this was a corridor air sample. The two exhaled condensate samples and the two expired air samples were negative. Interpretation: The faecal-derived aerosols in patients' toilets contained most of the detected SARS-CoV-2 virus in the hospital, highlighting the importance of surface and hand hygiene for intervention.


title: Transitioning Out of the Coronavirus Lockdown: A Framework for Evaluating Zone-Based Social Distancing

text: In the face of elevated pandemic risk, canonical epidemiological models imply the need for extreme social distancing over a prolonged period. Alternatively, people could be organized into zones, with more interactions inside their zone than across zones. Zones can deliver significantly lower infection rates, with less social distancing, particularly if combined with simple quarantine rules and contact tracing. This paper provides a framework for understanding and evaluating the implications of zones, quarantines, and other complementary policies.


title: One-pot Detection of COVID-19 with Real-time Reverse-transcription Loop-mediated Isothermal Amplification (RT-LAMP) Assay and Visual RT-LAMP Assay

text: Background Rapid and reliable diagnostic assays were critical for prevention and control of the coronavirus pneumonia caused by COVID-19. Objective This study was to establish one-pot real-time reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay and one-pot visual RT-LAMP assay for the detection of COVID-19. Methods Six specific LAMP primers targeting the N gene of COVID-19 were designed, the RT-LAMP reaction system was optimized with plasmid pUC57 containing N gene sequence, the detection limit was determined with a serial dilution of the plasmid pUC57 containing N gene sequence, and the one-pot real-time RT-LAMP assay and one-pot visual RT-LAMP assay for the detection of COVID-19 were established. Results Our results showed that the one-pot RT-LAMP assays can detect COVID-19 with a limit of ≥ 6 copies per μl−1 of pUC57 containing N gene sequence. Conclusion This study provides rapid, reliable and sensitive tools for facilitating preliminary and cost-effective prevention and control of COVID-19.


Coercion or the social contract? COVID 19 and spatial (in)justice in African cities


title: Analysis of influencing factors of death in patients with COVID-19/ 新型冠状病毒肺炎患者死亡影响因素分析

text: Objective: To analyze the influencing factors of death in patients with coronavirus disease 2019 (COVID-19) and provide a reference for clinically reducing the mortality of patients with COVID-19. Methods: Based on the retrospective analysis of the case data of all patients with COVID-19 admitted in our hospital from January 17th to February 25th, 2020, and the sex, age, whether or not to take Chinese medicine preparations during hospitalization, clinical classification, comorbidities, nucleic acid test results, admission time, discharge and other relevant indicators were collected for statistical analysis. Results: During the period of COVID-19, the number of patients of COVID-19 in our hospital gradually increased. At the epidemic peak period, 904 patients with COVID-19 were treated simultaneously. From January 17th to February 25th, 2020, a total of 1 305 patients with COVID-19 were treated in our hospital, including 632 males and 673 females, and the male to female ratio was 1:1.06. The age distribution ranged from 7 to 111 years, with a median of 63 (51, 70) years old. There was no significant difference in the age distribution of patients between different genders (Z = 1.217, P = 0.224). The results of univariate analysis showed that the patient's gender, age, whether to take Chinese medicine preparations during treatment, clinical classification, whether combined with underlying diseases (hypertension, coronary heart disease, diabetes, tumors and uremia) and nucleic acid test results all could affect patients fatality rate. Logistics multivariate regression analysis found that taking traditional Chinese medicine preparations, clinical classification, and whether combined with underlying diseases were independent risk factors for death in patients with COVID-19. Conclusion: The death of patients with COVID-19 is related to various factors. Reducing the occurrence of critical illness, controlling underlying diseases, stabilizing blood pressure and blood sugar, actively improving cardio-cerebral vascular conditions, and stabilizing renal function are main measures to improve the therapeutic effect, and early application of traditional Chinese medicine treatment also plays a very important role in reducing the mortality of patients with COVID-19.


title: Genomic Dissection of an Icelandic Epidemic of Equine Respiratory Disease

text: The native horse population of Iceland has remained free of major infectious diseases. Between May and July 2010 an epidemic of respiratory disease swept through the population. Initial microbiological investigations ruled out known equine viral agents as the cause of the infections, but identified the opportunistic pathogen Streptococcus zooepidemicus as being frequently isolated from diseased animals. This diverse bacterial species has a broad host range and is usually regarded as a commensal of horses. By genome sequencing S. zooepidemicus recovered from horses during the epidemic we show that although multiple clones of S. zooepidemicus were present in the population, one particular clone, ST209, was responsible for the epidemic. Concurrent with the epidemic, ST209 caused zoonotic infections, highlighting the pathogenic potential of this clone. Phylogenetic analysis suggests that the original ST209 strain entered Iceland in late 2008 or early 2009. Epidemiological investigation revealed that the incursion of this strain into a training yard that utilized a submerged treadmill between the 5th and 19th of February 2010 was a critical trigger for the ensuing epidemic of disease, provided a nidus for the infection of multiple horses, and subsequent distribution of these animals to multiple sites in Iceland.


title: Repurposing of Miglustat to inhibit the coronavirus Severe Acquired Respiratory Syndrome SARS-CoV-2

text: Repurposing clinically available drugs to treat the new coronavirus disease COVID-19 is an urgent need in these early stages of the SARS-CoV-2 pandemic, when very few treatment options are available. The iminosugar Miglustat is a well-characterized drug for the treatment of rare genetic lysosome storage diseases such as Gaucher and Niemann-Pick type C, and has also been described to be active against a variety of enveloped viruses. The activity of Miglustat is here demonstrated for SARS-CoV-2 at concentrations achievable in the plasma by current clinical regimens without cytotoxicity. The drug acts at the post-entry level and leads to a marked decrease of viral proteins and release of infectious virus. The mechanism resides in the inhibitory activity towards α-glucosidases that are involved in early stages of glycoprotein N-linked oligosaccharide processing in the endoplasmic reticulum, leading to a marked decrease of the viral Spike protein. The wealth of available data on the clinical use of Miglustat for the treatment of lysosomal storage disorders and the antiviral properties against SARS-CoV-2 make it an ideal candidate for drug repurposing.


title: Pulmonary embolism: yet another cause of hypoxaemic respiratory failure in COVID-19

text: Pulmonary embolism represents an overlooked cause of worsening respiratory failure in COVID-19. A regular bedside evaluation for atypical features like pleuritic chest pain or pleural effusion could help identify suspected cases for appropriate management. https://bit.ly/3bbBPqZ


title: Fight against COVID-19: A global outbreak response management performance view

text: Outbreak response can be viewed as a project for which the window of opportunity for planning is often quite limited Therefore, regular evaluation for sharing the lessons learned is crucial, especially in the cases of national and global crises As one of the major global concerns, the novel coronavirus, also known as COVID-19, has infected and killed many people in several countries worldwide Hence, it is worth analyzing the performance of different countries in this regard In this paper, the confirmed Case Fatality Rate (cCFR), and the confirmed Case Recovery Rate (cCRR) are considered as the main performance criteria, and the data are analyzed utilizing statistical confidence intervals (CIs) implemented in Python The results identify the regions with high cCFR and low cCRR, as well as the regions with low cCFR and high cCRR Finally, it is suggested to systematically transfer the knowledge and lessons learned from the high performing countries to where such information and knowledge is needed (C) 2020 by the authors;licensee Growing Science, Canada


title: A study on the relationship between BCG vaccination and Covid-19 prevalence: Do other confounders warrant investigation?

text: The Covid-19 pandemic, which originated from Wuhan, Hubei province, China, and quickly spread to the rest of the globe is caused by SARS-CoV-2, a single-stranded RNA virus. Preliminary data suggest a relationship between the BCG vaccine and the prevalence of Covid-19. The BCG vaccine is used in the prevention of tuberculosis, a disease that is most prevalent in developing countries. To determine the potential protective role of BCG vaccination, this study investigated the occurrence of Covid-19 and the relationship between the spread of Covid-19 in countries that offer BCG vaccination and those that do not. The study also performed a phylogenetic analysis of the strains involved in the Covid-19 outbreak from the representative countries. To achieve the objectives, the study utilized publicly available data on population size, vaccination coverage, and Covid-19 cases. Phylogenetic analysis was used to determine if some SARS-CoV-2 strains were more prevalent than others. The study revealed a significant negative trend between countries that offer the BCG vaccine to the general population and the reported cases of Covid-19. The study proposes future molecular and immunological analyses to determine the potential role of BCG vaccination in protection against Covid-19. This will determine if BCG has antiviral properties, with the possibility of recommending it for widespread use if supported by scientific data.


title: The coronavirus proofreading exoribonuclease mediates extensive viral recombination

text: Coronaviruses (CoVs) emerge as zoonoses and cause severe disease in humans, demonstrated by the SARS-CoV-2 (COVID-19) pandemic. RNA recombination is required during normal CoV replication for subgenomic mRNA (sgmRNA) synthesis and generates defective viral genomes (DVGs) of unknown function. However, the determinants and patterns of CoV recombination are unknown. Here, we show that divergent β-CoVs SARS-CoV-2, MERS-CoV, and murine hepatitis virus (MHV) perform extensive RNA recombination in culture, generating similar patterns of recombination junctions and diverse populations of DVGs and sgmRNAs. We demonstrate that the CoV proofreading nonstructural protein (nsp14) 3’-to-5’ exoribonuclease (nsp14-ExoN) is required for normal CoV recombination and that its genetic inactivation causes significantly decreased frequency and altered patterns of recombination in both infected cells and released virions. Thus, nsp14-ExoN is a key determinant of both high fidelity CoV replication and recombination, and thereby represents a highly-conserved and vulnerable target for virus inhibition and attenuation.


Low serum 25-hydroxyvitamin D (25D) levels in patients hospitalised with COVID-19 are associated with greater disease severity: results of a local audit of practice.


title: Possible effects of coronavurus infection (COVID-19) on the cardiovascular system/ ВЛИЯНИЕ КОРОНАВИРУСНОЙ ИНФЕКЦИИ (COVID-19) НА СЕРДЕЧНО-СОСУДИСТУЮ СИСТЕМУ

text: Acute viral respiratory infections can increase the risk of progression of a pre-existing condition, including a cardiovascular pathology. Life-threatening complications of Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) necessitate research into the cardiovascular effects of COVID-19 crucial for developing adequate treatment strategy for infected patients, especially those of advanced age. This article reviews the literature on the clinical and functional characteristics of patients with COVID-19, including those with poor outcomes. The article looks at the pathophysiological processes occurring in the cardiovascular system in the setting of SARS-CoV-2 infection, risk factors and death predictors. It also discusses continuation of therapy with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in patients with COVID-19.


title: Machine Learning Maps Research Needs in COVID-19 Literature

text: Summary Manually assessing the scope of the thousands of publications on the COVID-19 (coronavirus disease 2019) pandemic is an overwhelming task. Shortcuts through metadata analysis (e.g., keywords) assume that studies are properly tagged. However, machine learning approaches can rapidly survey the actual text of coronavirus abstracts to identify research overlap between COVID-19 and other coronavirus diseases, research hotspots, and areas warranting exploration. We propose a fast, scalable, and reusable framework to parse novel disease literature. When applied to the COVID-19 Open Research Dataset (CORD-19), dimensionality reduction suggested that COVID-19 studies to date are primarily clinical-, modeling- or field-based, in contrast to the vast quantity of laboratory-driven research for other (non-COVID-19) coronavirus diseases. Topic modeling also indicated that COVID-19 publications have thus far focused primarily on public health, outbreak reporting, clinical care, and testing for coronaviruses, as opposed to the more limited number focused on basic microbiology, including pathogenesis and transmission.


title: Beneficial effect of corticosteroids in severe COVID-19 pneumonia: a propensity score matching analysis.

text: Background. Since December 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), responsible for Coronavirus Disease 2019 (COVID-19), is spreading worldwide, causing significant morbidity and mortality. No specific treatment has yet clearly shown to improve the disease's evolution. Validated therapeutic options are urgently needed. Methods. In this retrospective study, we aimed to evaluate determinants of the prognosis of the disease in 70 patients with COVID-19 severe pneumonia (i.e. requiring at least 3 liters of oxygen) hospitalized between 10 March and 9 April, 2020, in the Centre Hospitalier Alpes Leman, France. The main outcome was oro-tracheal intubation and the exposure of interest was corticotherapy. Since this was not a randomized trial, we used propensity score matching to estimate average treatment effect. Results. There was evidence that corticotherapy lowered the risk of intubation with a risk difference of -47.1% (95% confidence interval -71.8% to -22.5%). Conclusion. Corticosteroid, a well-known, easily available, and cheap treatment, could be an important tool in management of severe COVID-19 patients with respiratory failure. Not only could it provide an individual benefit, but also, in the setting of the COVID-19 ongoing pandemic, lower the burden on our vulnerable healthcare systems.


title: Bats are key hosts in the radiation of mammal-associated Bartonella bacteria

text: Bats are notorious reservoirs of several zoonotic diseases and may be uniquely tolerant of infection among mammals. Broad sampling has revealed the importance of bats in the diversification and spread of viruses and eukaryotes to other animal hosts. Vector-borne bacteria of the genus Bartonella are prevalent and diverse in mammals globally and recent surveys have revealed numerous Bartonella lineages in bats. We assembled a sequence database of Bartonella strains, consisting of nine genetic loci from 209 previously characterized lineages and 121 new cultured strains from bats, and used these data to perform the most comprehensive phylogenetic analysis of Bartonella to date. This analysis included estimation of divergence dates using a molecular clock and ancestral reconstruction of host associations and geography. We estimate that Bartonella began infecting mammals 62 million years ago near the Cretaceous-Paleogene boundary. Additionally, the radiation of particular Bartonella clades correlate strongly to the timing of diversification and biogeography of mammalian hosts. Bats were inferred to be the ancestral hosts of all mammal-associated Bartonella and appear to be responsible for the early geographic expansion of the genus. We conclude that bats have had a deep influence on the evolutionary radiation of Bartonella bacteria and their spread to other mammalian orders. These results support a ‘bat seeding’ hypothesis that could explain similar evolutionary patterns in other mammalian parasite taxa. Application of such phylogenetic tools as we have used to other taxa may reveal the general importance of bats in the ancient diversification of mammalian parasites. Significance statement Discovering the evolutionary history of infectious agents in animals is important for understanding the process of host adaptation and the origins of human diseases. To clarify the evolution of the Bartonella genus, which contains important human pathogens, we performed phylogenetic analysis on a broad diversity of Bartonella strains, including novel strains from bats. Our results indicate that Bartonella clades diversified along with their mammal hosts over millions of years. Bats appear to be especially important in the early radiation and geographic dispersal of Bartonella lineages. These patterns are consistent with research indicating a chiropteran origin of important human viruses and eukaryotic parasites, suggesting that bats may play a unique role as historical sources of infections to other hosts.


title: N and O glycosylation of the SARS-CoV-2 spike protein

text: Covid-19 pandemic outbreak is the reason of the current world health crisis. The development of effective antiviral compounds and vaccines requires detailed descriptive studies of the SARS-CoV-2 proteins. The SARS-CoV-2 spike (S) protein mediates virion binding to the human cells through its interaction with the ACE2 cell surface receptor and is one of the prime immunization targets. A functional virion is composed of three S1 and three S2 subunits created by furin cleavage of the spike protein at R682, a polybasic cleavage sites that differs from the SARS-CoV spike protein of 2002. We observe that the spike protein is O-glycosylated on a threonine (T678) near the furin cleavage site occupied by core-1 and core-2 structures. In addition, we have identified eight additional O-glycopeptides on the spike glycoprotein and we confirmed that the spike protein is heavily N-glycosylated. Our recently developed LC-MS/MS methodology allowed us to identify LacdiNAc structural motifs on all occupied N-glycopeptides and polyLacNAc structures on six glycopeptides of the spike protein. In conclusion, our study substantially expands the current knowledge of the spike protein’s glycosylation and enables the investigation of the influence of the O-glycosylation on its proteolytic activation.


title: The impacts of diagnostic capability and prevention measures on transmission dynamics of COVID-19 in Wuhan

text: Background: Although the rapidly rising transmission trend of COVID-19 in Wuhan has been controlled in late February 2020, the outbreak still caused a global pandemic afterward. Understanding Wuhan COVID-19 transmission dynamics and the effects of prevention approaches is of significant importance for containing virus global transmission. However, most of the recent studies focused on the early outbreaks without considering improvements in diagnostic capability and effects of prevention measures together, thus the estimated results may only reflect the facts in a given period of time. Methods: We constructed a stochastic susceptible-exposed-infected-quarantined-recovered (SEIQR) model, embedding with latent periods under different prevention measures and proportions of documented infections to characterize the Wuhan COVID-19 transmission cross different stages of the outbreak. The epidemiological parameters were estimated using a particle filtering approach. Results: Our model successfully reproduced the dynamics of the Wuhan local epidemic with two peaks on February 4 and February 12 separately. Prevention measures determined the time of reaching the first peak and caused an 87% drop in the R_t from 3.09 (95% CI, 2.10 to 3.63) to 0.41 (95% CI, 0.18 to 0.66). An improved diagnostic capability created the second peak and increased the number of documented infections. The proportion of documented infections changed from 23% (95% CI, 20% to 26%) to 37% (95% CI, 33% to 41%) when the detection kits were released after January 26, and later up to 73% (95% CI, 64% to 80%) after the diagnostic criteria were improved.


title: A new transmission route for the propagation of the SARS-CoV-2 coronavirus

text: We explore here how variation in the SARS-CoV-2 virus tropism could influence epidemic spread. We use a compartmental model fit to the existing data. The model indicates that Wuhan quarantine measures were effective but that alternative virus forms (gut tropism) and a second propagation route (through environment) was present. For Singapore and Shenzhen region the secondary route does not seem to be active yet. Adequate prevention measures taking into account both routes should be implemented.


In and Out of the Hospital, Neurohospitalists Shift Course for the Surge in COVID-19


title: Thermographic detectability of porosity in multi-layered bare and anodized aluminum laser welds

text: Abstract This study investigates porosity detection by means of thermography in multi-layered laser welded aluminum joints. Samples with varying levels of porosity were created by laser welding bare or anodized aluminum material in multiple layers. For comparison, two Al 1100 top layer materials, one anodized and one bare, were welded in multiple layer configurations onto a 1.6 mm Al substrate. The samples were characterized by electrical measurements, tensile tests, and X-ray computed tomography imaging. Thermography was performed on the entire sample set, where the heat source distribution was used to analyze raw thermal data corresponding to the weld region-of-interest. A maximum peak histogram value of the thermography data was determined and was found to correlate well with the X-ray CT, electrical resistance, and tensile data. Thermography was observed to be more affected by pores close to the surface as confirmed by the porosity cross sections from the CT data. It was seen however, that in areas of many small pores, the overall thermography values indicated lower heat flow than other areas even if the individual pores could not be resolved. Overall it is shown that thermography correlates well with electrical resistance and tensile results, although more studies are needed to evaluate thicker stack-ups due to the limits placed by thermal diffusion.


title: COVID-19 IN INDIA: MODELLING, FORECASTING AND STATE-WISE COMPARISON

text: COVID-19 has turned the whole world upside down economically and socially. COVID-19 pandemic has caused around five crores of cases and three lakhs deaths globally as of 27 May 2020. This paper adopts four mathematical growth models. Basic models are encouraged because these models can make predictions with the available data and variables in the current scenario of COVID-19 pandemic. The best-fitted model is identified in accordance with the value of the coefficient of determination. As per the best model, there might be greater than 16 lakhs cases at the infection end in India. After predicting the future size of the pandemic, we analyzed how the disease severity varies among the Indian states and union territories using Case Fatality Rates (CFR).


title: Time is of the essence: impact of delays on effectiveness of contact tracing for COVID-19

text: Summary Background With confirmed cases of COVID-19 declining in many countries, lockdown measures are gradually being lifted. However, even if most social distancing measures are continued, other public health measures will be needed to control the epidemic. Contact tracing either via conventional methods or via mobile app technology is central to control strategies during de-escalation of social distancing. It is therefore essential to identify key factors for a contact tracing strategy (CTS) to be successful. Methods We evaluated the impact of timeliness and completeness in various steps of a CTS using a stochastic mathematical model with explicit time delays between time of infection, symptom onset, diagnosis by testing, and isolation. The model also includes tracing of close contacts (e.g. household members) and casual contacts with different delays and coverages. We computed effective reproduction numbers of a CTS (Rcts) for a population with social distancing measures and various scenarios for isolation of index cases and tracing and quarantine of its contacts. Findings In the best-case scenario (testing and tracing delays of 0 days and tracing coverage of 100%) the effective reproduction number will be reduced with 50% from 1.2 (with social distancing only) to 0.6 (Rcts) by contact tracing. A testing delay of 3 days requires tracing delay or coverage to be at most 1 day or at least 80% to keep Rcts below 1, with the Rcts reduction being 15% and 17%, respectively. With a testing delay of 4 days, even the most efficient CTS cannot reach Rcts values below 1. The effect of minimizing tracing delay (e.g., with app-based technology) declines with declining coverage of app use, but app-based tracing remains more effective than conventional contact tracing even with 20% coverage. The proportion of transmissions per index case that can be prevented depending on testing and tracing delay and isolation of index cases ranges from above 80% in the best-case scenario (testing and tracing delays of 0 days) to 40% and 17% with testing delays of 3 and 5 days, respectively. Interpretation Minimizing testing delay is of key importance for the effectiveness of CTS. Optimizing testing and tracing coverage and minimizing tracing delays, for instance with app-based technology further enhances effectiveness of CTS, with a potential to prevent up to 80% of all transmissions. The process of conventional contact tracing should be reviewed and streamlined, while mobile app technology may offer a tool for gaining speed in the process.


title: Modulation of Gut Microbiota, Short-Chain Fatty Acid Production, and Inflammatory Cytokine Expression in the Cecum of Porcine Deltacoronavirus-Infected Chicks

text: Porcine deltacoronavirus (PDCoV) is a novel swine enteropathogenic coronavirus that causes watery diarrhea and induces proinflammatory cytokine responses in piglets. Our previous research showed that the specific-pathogen-free (SPF) chicks exhibited mild diarrhea and low fecal viral shedding, along with cecum lesions after PDCoV infection. Disturbances in the homeostasis of the gut microbiota have been associated with various diseases. We aimed to explore the effects of PDCoV infection on chick gut microbiota, short-chain fatty acid (SCFAs) production, and inflammatory cytokine expression in chicks, and also to investigate the relationship between gut microbiota and SCFAs or inflammatory cytokine expression of the PDCoV-infected chicks. Results obtained using 16S rRNA sequencing showed that infection with PDCoV strain HNZK-02 significantly altered the composition of chick gut microbiota, with the reduced abundance of Eisenbergiella and Anaerotruncus genera at 5 days post-inoculation (dpi) (P < 0.05), and an increased abundance of Alistipes genus at 17 dpi (P < 0.05). The production of SCFAs in the cecum of PDCoV HNZK-02–infected chicks, including acetic acid, propionic acid, and butyric acid, decreased in all cases. The expression of inflammatory cytokines (interferon-γ, tumor necrosis factor-α, and interleukin-10) was increased in the cecum tissue and serum of the PDCoV HNZK-02–infected chicks when detected by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Further analysis showed significant correlation between bacterial genera and SCFAs or inflammatory cytokines expression in cecum of the PDCoV infected chicks. These findings might provide new insight into the pathology and physiology of PDCoV in chicks.


Sterling to produce hydroxychloroquine


title: Japanese citizens' behavioral changes and preparedness against COVID-19: How effective is Japan's approach of self-restraint?

text: The Japanese government instituted countermeasures against COVID-19, a pneumonia caused by the new coronavirus, in January 2020. Seeking “people's behavioral changes,” in which the government called on the public to take precautionary measures or exercise self-restraint, was one of the important strategies. The purpose of this study is to investigate how and from when Japanese citizens have changed their precautionary behavior under these circumstances, where the government has only requested their cooperation. This study uses micro data from a cross-sectional survey conducted on an online platform of an online research company, based on quota sampling that is representative of the Japanese population. By the end of March 2020, we had recruited a total of 11,342 respondents, aged from 20 to 64 years. About 85% reported practising the social distancing recommended by the government. More females than males and more older than younger participants are supportive of practicing social distancing. Frequent handwashing is conducted by 86 percent of all, 92 percent of female and 87.9 percent of over-40 participants. The most important event influencing these precautionary actions was the infection aboard the Diamond Princess cruise ship, which occurred in early February 2020 (23%). Information from the central and local governments, received by 60% of the participants, was deemed trustworthy by 50%. However, the results also showed that about 20% of the participants were reluctant to implement proper prevention measures. The statistical analysis indicated that the typical characteristics of those people were male, younger (under 30 years old), unmarried, from lower-income households, with a drinking or smoking habit and a higher extraversion score. To prevent the spread of infection in Japan, it is imperative to address these individuals and encourage their behavioral changes using various means to reach and influence them.


title: Rapid non- invasive detection of Influenza- A- infection by multicapillary column coupled ion mobility spectrometry

text: Infectious pathogens are a global issue. Global air travelling offers an easy and fast opportunity not only for people but also for infectious diseases to spread around the world within a few days. Therefore a rapid on-site screening of infected people is urgently needed. Due to the small size and easy handling, the ion mobility spectrometry coupled with a multicapillary column (MCC-IMS) is a very promising, sensitive method for the on-site identification of infectious pathogens based on scents, volatile organic compounds (VOCs). The purpose of this study was to prospectively assess whether differentiation between patients suffering from common cold and those from Influenza-A-infection based on VOCs with MCC-IMS is possible. Nasal breath was investigated in 24 consecutive patients suspected of having Influenza-A-infection by MCC-IMS. In 14 Influenza-A-infected patients, infection was proven by PCR of nasopharyngeal swabs. Ten patients with negative PCR diagnosis served as controls. For picking up relevant VOCs in MCC-IMS spectra, software based on cluster analysis followed by multivariate statistical analysis was applied. With only four VOCs canonical discriminant analysis was able to distinguish Influenza-A-infected patients from PCR- negative patients with 100% sensitivity and 100% specificity. This present proof-of-concept- study yields encouraging results showing a rapid diagnosis of viral infections in nasal breath within 5 minutes by MCC-IMS. The next step is to validate the results with a greater number of patients with Influenza-A-infection as well as other viral diseases. Registration number at ClinicalTrials.gov NCT04282135.


JLT and the Coronavirus


title: Effect of Workpiece Curvature on Axial Surface Error Profile in Flat End-Milling of Thin-walled Components

text: Abstract The advancements in the domain of CAD/CAM and CNC machine tools facilitated machining of complex geometric shapes to meet functional requirements and/or aesthetic appearances. These shapes combine several geometric features such as zero curvature (straight), constant curvature (circular) and variable curvature surfaces. The components often contain thin-walled sections having inherently lower stiffness that induces static deflections transforming into surface error and violation of error limits specified by the designer. This paper presents a comparison of deflection induced surface error profile generated during the end milling of zero and constant curvature thin-walled components. The proposed framework incorporates computational model to estimate cutting forces, Finite Element Analysis (FEA) model to compute workpiece deflections, and surface generation mechanism to derive error profile. The paper also investigates the effect of change in the radial engagement area due to workpiece curvature by introducing the concept of ‘Equivalent Radial Depth of Cut’. Further, the effect of change in workpiece curvature is investigated on the surface error profile in the paper. The proposed framework has been generalized to accommodate the variation of workpiece geometry, and the results are validated by conducting a set of end milling experiments.


title: SARS-CoV-2 Whole Genome Amplification and Sequencing for Effective Population-Based Surveillance and Control of Viral Transmission

text: Background With the gradual reopening of economies and resumption of social life, robust surveillance mechanisms should be implemented to control the ongoing COVID-19 pandemic. Unlike RT-qPCR, SARS-CoV-2 Whole Genome Sequencing (cWGS) has the added advantage of identifying cryptic origins of the virus, and the extent of community-based transmissions versus new viral introductions, which can in turn influence public health policy decisions. However, practical and cost considerations of cWGS should be addressed before it can be widely implemented. Methods We performed shotgun transcriptome sequencing using RNA extracted from nasopharyngeal swabs of patients with COVID-19, and compared it to targeted SARS-CoV-2 full genome amplification and sequencing with respect to virus detection, scalability, and cost-effectiveness. To track virus origin, we used open-source multiple sequence alignment and phylogenetic tools to compare the assembled SARS-CoV-2 genomes to publicly available sequences. Results We show a significant improvement in whole genome sequencing data quality and viral detection using amplicon-based target enrichment of SARS-CoV-2. With enrichment, more than 99% of the sequencing reads mapped to the viral genome compared to an average of 0.63% without enrichment. Consequently, a dramatic increase in genome coverage was obtained using significantly less sequencing data, enabling higher scalability and significant cost reductions. We also demonstrate how SARS-CoV-2 genome sequences can be used to determine their possible origin through phylogenetic analysis including other viral strains. Conclusions SARS-CoV-2 whole genome sequencing is a practical, cost-effective, and powerful approach for population-based surveillance and control of viral transmission in the next phase of the COVID-19 pandemic.


title: A systems approach to inflammation identifies therapeutic targets in SARS-CoV-2 infection

text: Background Infection with SARS-CoV-2 manifests itself as a mild respiratory tract infection in the majority of individuals, which progresses to a severe pneumonia and acute respiratory distress syndrome (ARDS) in 10-15% of patients. Inflammation plays a crucial role in the pathogenesis of ARDS, with immune dysregulation in severe COVID-19 leading to a hyperinflammatory response. A comprehensive understanding of the inflammatory process in COVID-19 is lacking. Methods In this prospective, multicenter observational study, patients with PCR-proven or clinically presumed COVID-19 admitted to the intensive care unit (ICU) or clinical wards were included. Demographic and clinical data were obtained and plasma was serially collected. Concentrations of IL-6, TNF-, complement components C3a, C3c and the terminal complement complex (TCC) were determined in plasma by ELISA. Additionally, 269 circulating biomarkers were assessed using targeted proteomics. Results were compared between ICU and non ICU patients. Findings A total of 119 (38 ICU and 91 non ICU) patients were included. IL-6 plasma concentrations were elevated in COVID-19 (ICU vs. non ICU, median 174.5 pg/ml [IQR 94.5-376.3 vs. 40.0 pg/ml [16.5-81.0]), whereas TNF- concentrations were relatively low and not different between ICU and non ICU patients (median 24.0 pg/ml [IQR 16.5-33.5] and 21.5 pg/ml [IQR 16.0-33.5], respectively). C3a and terminal complement complex (TCC) concentrations were significantly higher in ICU vs. non ICU patients (median 556.0 ng/ml [IQR 333.3-712.5]) vs. 266.5 ng/ml [IQR 191.5-384.0 for C3a and 4506 mAU/ml [IQR 3661-6595 vs. 3582 mAU/ml [IQR 2947-4300] for TCC) on the first day of blood sampling. Targeted proteomics demonstrated that IL-6 (logFC 2.2), several chemokines and hepatocyte growth factor (logFC 1.4) were significantly upregulated in ICU vs. non ICU patients. In contrast, stem cell factor was significantly downregulated (logFC -1.3) in ICU vs. non ICU patients, as were DPP4 (logFC -0.4) and protein C inhibitor (log FC -1.0), the latter two factors also being involved in the regulation of the kinin-kallikrein pathway. Unsupervised clustering pointed towards a homogeneous pathogenetic mechanism in the majority of patients infected with SARS-CoV-2, with patient clustering mainly based on disease severity. Interpretation We identified important pathways involved in dysregulation of inflammation in patients with severe COVID-19, including the IL-6, complement system and kinin-kallikrein pathways. Our findings may aid the development of new approaches to host-directed therapy.


title: Increased PCR screening capacity using a multi-replicate pooling scheme

text: Effective public health response to viral outbreaks such as SARS-CoV-2 is often informed by real-time PCR screening of large populations. Pooling samples can increase screening capacity. However, when a traditional pool is tested positive, all samples in the pool need individual retesting, which becomes ineffective at a higher proportion of positive samples. Here, we report a new pooling protocol that mitigates this problem by replicating samples across multiple pools. The resulting pool set allows the sample status to be resolved more often than with traditional pooling. At 2% prevalence and 20 samples per pool, our protocol increases screening capacity by factors of 5 and 2 compared to individual testing and traditional pooling, respectively. The corresponding software to layout and resolve samples is freely available under a BSD license (https://github.com/phiweger/clonepool).


title: Global COVID-19 fatality analysis reveals Hubei-like countries potentially with severe outbreaks

text: 1. CFR in Iran in the early stage of the outbreak is the highest among all the countries 2. CFRs in the USA and Italy are similar to that in Hubei Province in the early stage of the outbreak. 3. CFRs in South Korea are similar to that outside Hubei (in China), indicating less severe outbreaks therein. 4. Our findings highlight the potential severity of outbreaks globally, particular in the USA.


title: Lockdowns to Contain COVID-19 Increase Risk and Severity of Mosquito-Borne Disease Outbreaks

text: Many countries are implementing lockdown measures to slow the COVID-19 pandemic, putting more than a third of the world's population under restrictions. The scale of such lockdowns is unprecedented, and while some effects of lockdowns are readily apparent, it is less clear what effects they may have on outbreaks of serious communicable diseases. We examine the impact of these lockdowns on outbreaks of mosquito-borne diseases. Using an agent-based model and simulations, we find that the risk and severity of such outbreaks is much greater under lockdown conditions, with the number of infected people doubling in some cases. This increase in number of cases varies by different mosquito-borne diseases, and is significantly higher for diseases spread by day-biting mosquitoes. We analysed various intervention strategies and found that during lockdowns, decentralised strategies such as insecticide-treated nets and indoor residual spraying are more effective than centralised strategies.


title: Applying the SEIR Model in Forecasting The COVID-19 Trend in Malaysia: A Preliminary Study

text: On March 18, 2020 the Malaysian government implemented a 14-day Movement Control Order (MCO) as part of the mitigation plan in controlling the COVID-19 epidemic in the country. The MCO aims to limit the contact rates among the population and hence prevent the surge of infected individuals. However, the trend of the epidemic before and after the MCO was not apparent. By applying the Susceptible, Exposed, Infectious and Removed (SEIR) mathematical model, we aimed to forecast the trend of COVID-19 epidemic in Malaysia using data from March 17 to 27, 2020. Based on several predetermined assumptions, the results of the analyses showed that after the implementation of the 14-day MCO from March 18 to 31, 2020, it is forecasted that the epidemic in Malaysia will peak approximately in the end of April 2020 and will subside by about the first week of July 2020. The MCO will flatten the epidemic curve but will prolong the duration of the epidemic. Decision to extend the duration of the MCO should depend on the consideration of socioeconomic factors as well. Keywords: SEIR model, COVID-19, forecasting, trend, Malaysia


title: Extended SIR prediction of the epidemics trend of COVID-19 in Italy and compared with Hunan, China

text: Background: Coronavirus Disease 2019 (COVID19) is currently a global public health threat. Outside of China, Italy is one of the most suffering countries with the COVID19 epidemic. It is important to predict the epidemics trend of COVID19 epidemic in Italy to help develop public health strategies. Methods: We used time series data of COVID 19 from Jan 22,2020 to Mar 16,2020. An infectious disease dynamic extended susceptible infected removed (eSIR) model, which covers the effects of different intervention measures in dissimilar periods, was applied to estimate the epidemic trend in Italy. The basic reproductive number was estimated using Markov Chain Monte Carlo methods and presented using the resulting posterior mean and 95% credible interval (CI). Hunan, with similar total number of populations in Italy, was used as a comparative item. Results: In the eSIR model, we estimated that the basic reproductive number for COVID 19 was respectively 4.10 (95% CI: 2.15 to 6.77) in Italy and 3.15(95% CI: 1.71 to 5.21) in Hunan. There would be totally 30 086 infected cases (95%CI:7920-81 869) under the current country blockade and the endpoint would be Apr 25 (95%CI: Mar 30 to Aug 07) in Italy. If the country blockade is imposed 5 day later, the total number of infected cases would expand the infection scale 1.50 times. Conclusion: Italy's current strict measures can efficaciously prevent the further spread of COVID19 and should be maintained. Necessary strict public health measures be implemented as soon as possible in other European countries with a high number of COVID19 cases. The most effective strategy needs to be confirmed in further studies.


title: COVID-19 outbreak at a large homeless shelter in Boston: Implications for universal testing

text: The circumstances of homelessness create the potential for rapid transmission of SARS-CoV-2 in this vulnerable population. Upon observing a cluster of COVID-19 cases from a single large homeless shelter in Boston, Boston Health Care for the Homeless Program conducted symptom assessments and polymerase chain reaction (PCR) testing for SARS-CoV-2 among all guests residing at the shelter over a 2-day period. Of 408 participants, 147 (36.0%) were PCR-positive for SARS-CoV-2. COVID-positive individuals were more likely to be male (p<0.001) but did not differ significantly from COVID-negative individuals with respect to other demographic and clinical characteristics. Cough (7.5%), shortness of breath (1.4%), and fever (0.7%) were all uncommon among COVID-positive individuals. Our findings illustrate the rapidity with which COVID-19 can be widely transmitted in a homeless shelter setting and suggest that universal PCR testing, rather than a symptom triggered approach, may be a better strategy for identifying and mitigating COVID-19 among people experiencing homelessness.


title: Trained, ready but under-utilised: Using student paramedics during a pandemic

text: The aim of this commentary is to outline a case for student paramedics as a potential solution to the operational resource issues ambulances services and other healthcare institutions are expected to experience during high demand situations, such as pandemics.


title: Ultrastructural analysis of SARS-CoV-2 interactions with the host cell via high resolution scanning electron microscopy

text: SARS-CoV-2 is the cause of the ongoing COVID-19 pandemic. Here, we investigated the interaction of this new coronavirus with Vero cells using high resolution scanning electron microscopy. Surface morphology, the interior of infected cells and the distribution of viral particles in both environments were observed 2 and 48 hours after infection. We showed areas of viral processing, details of vacuole contents, and viral interactions with the cell surface. Intercellular connections were also approached, and viral particles were adhered to these extensions suggesting direct cell-to-cell transmission of SARS-CoV-2. Highlights We used high resolution scanning electron microscopy to investigate Vero cells infected with SARS-CoV-2 at 2 and 48 hours post-infection. The central conclusions of this work include: Infected cells display polarization of their cytosol forming a restricted viroplasm-like zone dedicated to virus production and morphogenesis. This is the first demonstration of SARS-CoV-2 attachment by scanning electron microscopy. This is the first scanning electron microscopy images of the interior of SARS-CoV-2 infected cells and exploration of their vacuole contents. Perspective-viewing of bordering vesicles in close association with vacuoles. Observation of membrane ruffles and structures suggestive of exocytosis on the surface of infected cells. The first demonstration of viral surfing in cell-to-cell communication on SARS-CoV-2 infection.


title: Outbreak dynamics of COVID-19 in China and the United States

text: On March 11, 2020, the World Health Organization declared the coronavirus disease 2019, COVID-19, a global pandemic. In an unprecedented collective effort, massive amounts of data are now being collected worldwide to estimate the immediate and long-term impact of this pandemic on the health system and the global economy. However, the precise timeline of the disease, its transmissibility, and the effect of mitigation strategies remain incompletely understood. Here we integrate a global network model with a local epidemic SEIR model to quantify the outbreak dynamics of COVID-19 in China and the United States. For the outbreak in China, in n=30 provinces, we found a latent period of 2.56+/-0.72 days, a contact period of 1.47+/-0.32 days, and an infectious period of 17.82+/-2.95 days. We assume that the latent and infectious periods are disease-specific and the contact period is behavior-specific and can vary between different communities, states, or countries. For the early stages of the outbreak in the United States, in n=50 states, we adopted the latent and infectious periods from China, and found a contact period of 3.38+/-0.69 days. Our network model predicts that - without the massive political mitigation strategies that are in place today - the United states would have faced a basic reproduction number of 5.3+/-0.95 and a nationwide peak of the outbreak on May 10, 2020 with 3 million infections. Our results demonstrate how mathematical modeling can help estimate outbreak dynamics and provide decision guidelines for successful outbreak control. We anticipate that our model will become a valuable tool to estimate the potential of vaccination and quantify the effect of relaxing political measures including total lock down, shelter in place, and travel restrictions for low-risk subgroups of the population or for the population as a whole.


title: A Pipeline for Faecal Host DNA Analysis by Absolute Quantification of LINE-1 and Mitochondrial Genomic Elements Using ddPCR

text: Stool contains DNA shed from cells of the gastrointestinal (GI) tract and has great potential as a bio-specimen for non-invasive, nucleic acid-based detection of GI diseases. Whereas methods for studying faecal microbiome DNA are plentiful, there is a lack of well-characterised procedures for stabilisation, isolation, and quantitative analysis of faecal host DNA. We report an optimised pipeline for faecal host DNA analysis from the point-of-collection to droplet digital PCR (ddPCR) absolute quantification of host-specific gene targets. We evaluated multiple methods for preservation and isolation of host DNA from stool to identify the highest performing methods. To quantify host DNA even if present in partially degraded form, we developed sensitive, human-specific short-amplicon ddPCR assays targeting repetitive nuclear genomic elements (LINE-1) and mitochondrial genes. We validated the ability of these optimised methods to perform absolute quantification of host DNA in 200 stool DNA extracts from samples that were serially collected from three healthy individuals and three hospitalised patients. These specimens allowed assessment of host DNA day-to-day variability in stool specimens with widely varying physical characteristics (i.e., Bristol scores). We further extended this approach to mouse stool analysis, to enable faecal host DNA studies in animal disease models as well.


title: Racial and Ethnic Disparities in Population Level Covid-19 Mortality

text: Background: Current reporting of Covid-19 mortality data by race and ethnicity across the United States could bias our understanding of population-mortality disparities. Moreover, stark differences in age distribution by race and ethnicity groups are seldom accounted for in analyses. Methods: To address these gaps, we conducted a cross-sectional study using publicly-reported Covid-19 mortality data to assess the quality of race and ethnicity data (Black, Latinx, white), and estimated age-adjusted disparities using a random effects meta-analytic approach. Results: We found only 28 states, and NYC, reported race and ethnicity-stratified Covid-19 mortality along with large variation in the percent of missing race and ethnicity data by state. Aggregated relative risk of death estimates for Black compared to the white population was 3.57 (95% CI: 2.84-4.48). Similarly, Latinx population displayed 1.88 (95% CI: 1.61-2.19) times higher risk of death than white patients. Discussion: In states providing race and ethnicity data, we identified significant population-level Covid-19 mortality disparities. We demonstrated the importance of adjusting for age differences across population groups to prevent underestimating disparities in younger population groups. The availability of high-quality and comprehensive race and ethnicity data is necessary to address factors contributing to inequity in Covid-19 mortality.


title: Ecologic correlation between underlying population level morbidities and COVID-19 case fatality rate among countries infected with SARS-CoV-2

text: Background: The ongoing Coronavirus disease 2019 (COVID-19) pandemic is unprecedented in scope. High income countries (HIC) seemingly account for the majority of the mortalities considering that these countries have screened more persons. Low middle income countries (LMIC) countries may experience far worse mortalities considering the existence of a weaker health care system and the several underlying population level morbidities. As a result, it becomes imperative to understand the ecological correlation between critical underlying population level morbidities and COVID-19 case fatality rates (CFR). Method: This is an ecological study using data on COVID-19 cases, prevalence of COPD, prevalence of tobacco use, adult HIV prevalence, quality of air and life expectancy. We plotted a histogram, performed the Shapiro-Wilk normality test and used spearman correlation to assess the degree of correlation between COVID-19 case fatality rate (CFR) and other covariates mentioned above. Result: As at the 31st of March 2020, there were a total of 846,281 cases of COVID-19 from 204 countries and a global case fatality rate of 5% (range 0% to 29%). Angola and Sudan both had the highest CFR of 29%, while Italy had the highest number of deaths (i.e. 12,428) as at 31st of March 2020. Adult HIV prevalence has a significant but weak negative correlation with CFR (correlation coefficient = - 0.24, p value =0.01) while all the other variables have positive correlation with CFR due to COVID-19 though not statistically significant. Of the 204 countries analyzed, only 11 countries (i.e. 5%) had complete datasets across all 5 population level morbidities (i.e. prevalence of COPD, prevalence of tobacco use, life expectancy, quality of air, and adult HIV prevalence variables). Correlations of CFR from these 11 countries were similar to that from the 204 countries except for the correlation with quality of air and prevalence of tobacco use. Conclusion: While we interpret our data with caution given the fact that this is an ecological study, our findings suggest that population level factors such as prevalence of COPD, prevalence of tobacco use, life expectancy and quality of air are positively correlated with CFR from COVID-19 but, adult HIV prevalence has a weak and negative correlation with COVID-19 CFR and would require extensive research.


title: Evaluation of Group Testing for SARS-CoV-2 RNA

text: During the current COVID-19 pandemic, testing kit and RNA extraction kit availability has become a major limiting factor in the ability to determine patient disease status and accurately quantify prevalence. Current testing strategies rely on individual tests of cases matching restrictive diagnostic criteria to detect SARS-CoV-2 RNA, limiting testing of asymptomatic and mild cases. Testing these individuals is one effective way to understand and reduce the spread of COVID-19. Here, we develop a pooled testing strategy to identify these low-risk individuals. Drawing on the well-studied group testing literature, modeling suggests practical changes to testing protocols which can reduce test costs and stretch a limited test kit supply. When most tests are negative, pooling reduces the total number of tests up to four-fold at 2% prevalence and eight-fold at 0.5% prevalence. At current SARS-CoV-2 prevalence, randomized group testing optimized per country could double the number of tested individuals from 1.8M to 3.6M using only 672k more tests. This strategy is well-suited to supplement testing for asymptomatic and mild cases who would otherwise go untested, and enable them to adopt behavioral changes to slow the spread of COVID-19.


title: Lending a machine to combat COVID-19

text: The UK pharmaceutical services firm Sygnature Discovery is loaning its Tecan multisample automated pipetting machine to a network of government labs for testing COVID-19 The machine will enable rapid multiple sample analysis Sygnature had been using the machine for chemical library development but will scale back that work while it is on loan The company has also created an antiviral drug discovery team to support firms seeking compounds to combat COVID-19


Responding to Healthcare Disparities and Challenges With Access to Care During COVID-19


title: Modelling suggests blood group incompatibility may substantially reduce SARS-CoV-2 transmission

text: Several independent datasets suggest blood type A is over-represented and type O under-represented among COVID-19 patients. Here, I model a scenario in which ABO transfusion incompatibility reduces the chance of a patient transmitting the virus to an incompatible recipient. Comparison of model outputs to published data on COVID-19 prevalence indicates that if this scenario holds true, ABO incompatibility may reduce virus transmissibility by 60% or more. Paradoxically, however, targeted vaccination of either high-susceptibility type A or "super-spreader" type O individuals is less effective than random vaccination at blocking community spread of the virus. Instead, the key is to maintain blood type diversity amongst the remaining susceptible individuals. I stress that these results illustrate a theoretical model of ABO blood group interaction with virus transmission and require confirmation by observation.


title: Risk factors for severe corona virus disease 2019 (COVID-19) patients : a systematic review and meta analysis

text: Importance: With the increasing number of infections for COVID-19, the global health resources are deficient. At present, we don't have specific medicines or vaccines against novel coronavirus pneumonia (NCP) and our assessment of risk factors for patients with severe pneumonia was limited. In order to maximize the use of limited medical resources, we should distinguish between mild and severe patients as early as possible. Objective: To systematically review the evidence of risk factors for severe corona virus disease 2019 (COVID-19) patients. Evidence Review: We conducted a comprehensive search for primary literature in both Chinese and English electronic bibliographic data bases including China National Knowledge Infrastructure (CNKI), Wanfang, Weipu, Chinese Biomedicine Literature Database (CBM-SinoMed), MEDLINE (via PubMed), EMBASE, Cochrane Central Register, and Web of science. The American agency for health research and quality (AHRQ) tool were used for assessing risk of bias. Mata-analysis was undertaken using STATA version 15.0. Results: 20 articles (N=4062 participants) were eligible for this systematic review and meta-analysis. First in this review and meta-analysis, we found that elderly male patients with a high body mass index, high breathing rate and a combination of underlying diseases (such as hypertension, diabetes, cardiovascular disease, and chronic obstructive pulmonary disease) were more likely to develop into critically ill patients. second, compared with ordinary patients, severe patients had more significant symptom such as fever and dyspnea. Besides, the laboratory test results of severe patients had more abnormal than non-severe patients, such as the elevated levels of white-cell counts, liver enzymes, lactate dehydrogenase, creatine kinase, c-reactive protein and procalcitonin, etc, while the decreased levels of lymphocytes and albumin, etc. Interpretation: This is the first systematic review investigating the risk factors for severe corona virus disease 2019 (COVID-19) patients. The findings are presented and discussed by different clinical characteristics. Therefore, our review may provide guidance for clinical decision-making and optimizes resource allocation.


title: Early, low-dose and short-term application of corticosteroid treatment in patients with severe COVID-19 pneumonia: single-center experience from Wuhan, China

text: Background: Severe patients with 2019 novel coronavirus (2019-nCoV) pneumonia progressed rapidly to acute respiratory failure. We aimed to evaluate the definite efficacy and safety of corticosteroid in the treatment of severe COVID-19 pneumonia. Methods: Forty-six hospitalized patients with severe COVID-19 pneumonia hospitalized at Wuhan Union Hospital from January 20 to February 25, 2020, were retrospectively reviewed. The patients were divided into two groups based on whether they received corticosteroid treatment. The clinical symptoms and chest computed tomography(CT) results were compared. Results: A total of 26 patients received intravenous administration of methylprednisolone with a dosage of 1-2mg/kg/d for 5-7 days, while the remaining patients not. There was no significant difference in age, sex, comorbidities, clinical or laboratory parameters between the two groups on admission. The average number of days for body temperature back to the normal range was significantly shorter in patients with administration of methylprednisolone when compared to those without administration of methylprednisolone (2.06 ± 0.28 vs. 5.29 ± 0.70, P=0.010). The patients with administration of methylprednisolone had a faster improvement of SpO2, while patients without administration of methylprednisolone had a significantly longer interval of using supplemental oxygen therapy (8.2days[IQR 7.0-10.3] vs. 13.5days(IQR 10.3-16); P<0.001). In terms of chest CT, the absorption degree of the focus was significantly better in patients with administration of methylprednisolone. Conclusion: Our data indicate that in patients with severe COVID-19 pneumonia, early, low-dose and short-term application of corticosteroid was associated with a faster improvement of clinical symptoms and absorption of lung focus.


title: COVID-19 and Acute Kidney Injury requiring Kidney Replacement Therapy: A Bad Prognostic Sign.

text: The development of acute kidney injury in patients with COVID-19 is estimated to about 0.5% from earlier studies from China. The incidence of AKI in patients with COIVID-19 in the largest inpatient series in the United States is 22.2%3. Development of AKI requiring kidney replacement therapy in hospitalized patients is a bad prognostic sign. Out of Fifty patients admitted to our hospital with COVID-19 13/50(26%) developed AKI. All patients required hospitalization in intensive care unit care and 12/13 required initiation of kidney replacement therapy. The median age was 41 years (31-85 years) and 50% were men. Common comorbidities were obesity (83%), diabetes (42%), and hypertension (25%). 10/12 (83%) patients were hypoxemic and required oxygen therapy. 11/12 (92%) patients required invasive ventilation. Majority of patients had elevated neutrophils counts (81.8%) and low lymphocyte counts (81.8%). All patients had chest x-ray findings suggestive of pneumonia. 11/12(91.6%) developed septic shock requiring vasopressors. Review of UA showed all patient (9/9) had active urine sediments with blood but 7/9 of them have sterile pyuria. At the end of study period, 1 patient remained hospitalized. 10/11(90%) patients died and one patient was discharged home with resolution of AKI. Median length of stay was 13 days. The exact mechanism of AKI is not well understood in COVID-19 but can be due to acute tubular necrosis due to septic shock because of cytokine storm in severe COVID-19 or direct invasion by SARS-CoV-2 on podocytes and proximal renal tubular cells. Our findings suggest poor prognosis despite continuous kidney replacement therapies in patients who develop AKI with COVID-19.


title: No evidence of viral polymorphisms associated with Paediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2 (PIMS-TS).

text: Generally, children and teenagers do not become seriously ill with COVID-19. However, in countries with high rates of coronavirus disease, children with the syndrome COVID-19 associated inflammation syndrome referred to as PIMS-TS have been reported. Similarities noted between SARS-CoV-2 Spike protein sequences and those of other super antigens has prompted the suggestion that this might be the mechanism by SARS-CoV-ST triggers PIMS-TS. It has also been suggested that the D614G variant found more commonly in the US and across European countries may explain why PIMS-TS appears to be common in these countries. Here we analysed viral sequences from 13 paediatric COVID-19 patients of whom five were diagnosed with PIMS-TS. This is the first characterisation of viruses from PIMS-TS patients. In contrast to what has been hypothesised, we found no evidence of unique sequences associated with the viruses from PIMS-TS patients.


title: The Effect of Large-Scale Anti-Contagion Policies on the Coronavirus (COVID-19) Pandemic

text: Governments around the world are responding to the novel coronavirus (COVID-19) pandemic with unprecedented policies designed to slow the growth rate of infections. Many actions, such as closing schools and restricting populations to their homes, impose large and visible costs on society. In contrast, the benefits of these policies, in the form of infections that did not occur, cannot be directly observed and are currently understood through process-based simulations. Here, we compile new data on 1,659 local, regional, and national anti-contagion policies recently deployed in the ongoing pandemic across localities in China, South Korea, Iran, Italy, France, and the United States (US). We then apply reduced-form econometric methods, commonly used to measure the effect of policies on economic growth, to empirically evaluate the effect that these anti-contagion policies have had on the growth rate of infections. In the absence of any policy actions, we estimate that early infections of COVID-19 exhibit exponential growth rates of roughly 42% per day. We find that anti-contagion policies collectively have had significant effects slowing this growth. Our results suggest that similar policies may have different impacts on different populations, but we obtain consistent evidence that the policy packages now deployed are achieving large, beneficial, and measurable health outcomes. We estimate that, to date, current policies have already prevented or delayed on the order of 62 million infections across these six countries. These findings may help inform whether or when these ongoing policies should be lifted or intensified, and they can support decision-making in the other 180+ countries where COVID-19 has been reported.


title: Factors Associated with Access and Use of PPE during COVID-19: A Cross-sectional Study of Italian Physicians

text: Objectives During the course of the Novel Coronavirus (SARS-CoV-2) pandemic, Italy has reported one of the highest number of infections. Nearly ten percent of reported coronavirus infections in Italy occurred in healthcare workers. This study aimed to understand physicians access to personal protective equipment (PPE) and to information about their use, risk perception and strategies adopted to prevent contracting the infection. Methods We undertook a cross-sectional, online self-reported survey implemented between March 31 and April 5 2020 of Italian physicians. Results Responses were received from 529 physicians, only 13% of which reported to have access to PPE every time they need them. Approximately half of the physicians reported that the information received about the use of PPE was either clear (47%) or complete (54%). Risk perception about contracting the infection was influenced by receiving adequate information on the use of PPE. Access to adequate information on the use of PPE was associated with better ability to perform donning and doffing procedures [OR=2.2 95% C.I. 1.7-2.8] and reduced perception of risk [OR=0.5, 95% C.I. 0.4-0.6]. Conclusions Results from this rapid survey indicate that while ramping up supplies on PPE for healthcare workers is certainly of mandatory importance, adequate training and clear instructions are just as important.


BJUI Compass in the COVID era


title: Risk Prediction and Assessment: Duration, Infections, and Death Toll of the COVID-19 and Its Impact on China’s Economy

text: This study first analyzes the national and global infection status of the Coronavirus Disease that emerged in 2019 (COVID-19) It then uses the trend comparison method to predict the inflection point and Key Point of the COVID-19 virus by comparison with the severe acute respiratory syndrome (SARS) graphs, followed by using the Autoregressive Integrated Moving Average model, Autoregressive Moving Average model, Seasonal Autoregressive Integrated Moving-Average with Exogenous Regressors, and Holt Winter’s Exponential Smoothing to predict infections, deaths, and GDP in China Finally, it discusses and assesses the impact of these results This study argues that even if the risks and impacts of the epidemic are significant, China’s economy will continue to maintain steady development


title: Repurposing Pyramax® for the Treatment of Ebola Virus Disease: Additivity of the Lysosomotropic Pyronaridine and Non-Lysosomotropic Artesunate

text: We have recently identified three molecules (tilorone, quinacrine and pyronaridine tetraphosphate) which all demonstrated efficacy in the mouse model of infection with mouse-adapted Ebola virus (EBOV) model of disease and had similar in vitro inhibition of an Ebola pseudovirus (VSV-EBOV-GP), suggesting they interfere with viral entry. Using a machine learning model to predict lysosomotropism these compounds were evaluated for their ability to inhibit via a lysosomotropic mechanism in vitro. We now demonstrate in vitro that pyronaridine tetraphosphate is an inhibitor of Lysotracker accumulation in lysosomes (IC50 = 0.56 μM). Further, we evaluated synergy between pyronaridine and artesunate (Pyramax®), which are used in combination to treat malaria. Artesunate was not found to have lysosomotropic activity in vitro and the combination effect on EBOV inhibition was shown to be additive. Pyramax® may represent a unique example of the repurposing of a combination product for another disease.


title: Towards the design of multiepitope-based peptide vaccine candidate against SARS-CoV-2

text: Coronavirus disease 2019 is a current pandemic health threat especially for elderly patients with comorbidities. This respiratory disease is caused by a beta coronavirus known as severe acute respiratory syndrome coronavirus 2. The disease can progress into acute respiratory distress syndrome that can be fatal. Currently, no specific drug or vaccine are available to combat this pandemic outbreak. Social distancing and lockdown have been enforced in many places worldwide. The spike protein of coronavirus 2 is essential for viral entry into host target cells via interaction with angiotensin converting enzyme 2. This viral protein is considered a potential target for design and development of a drug or vaccine. Previously, we have reported several potential epitopes on coronavirus 2 spike protein with high antigenicity, low allergenicity and good stability against specified proteases. In the current study, we have constructed and evaluated a peptide vaccine from these potential epitopes by using in silico approach. This construct is predicted to have a protective immunogenicity, low allergenicity and good stability with minor structural flaws in model build. The population coverage of the used T-cells epitopes is believed to be high according to the employed restricted alleles. The vaccine construct can elicit efficient and long-lasting immune response as appeared through simulation analysis. This multiepitope-based peptide vaccine may represent a potential candidate against coronavirus 2. However, further in vitro and in vivo verification are required.


title: An Adaptive, Interacting, Cluster-Based Model Accurately Predicts the Transmission Dynamics of COVID-19

text: The SARS-CoV-2 driven disease, COVID-19, is presently a pandemic with increasing human and monetary costs. COVID-19 has put an unexpected and inordinate degree of pressure on healthcare systems of strong and fragile countries alike. In order to launch both containment and mitigation measures, each country requires accurate estimates of COVID-19 incidence as such preparedness allows agencies to plan efficient resource allocation and design control strategies. Here, we have developed a new adaptive, interacting, and cluster-based mathematical model to predict the granular trajectory COVID-19. We have analyzed incidence data from three currently afflicted countries of Italy, the United States of America, and India, and show that our approach predicts state-wise COVID-19 spread for each country with high accuracy. We show that R0 as the basic reproduction number exhibits significant spatial and temporal variation in these countries. However, by including a new function for temporal variation of R0 in an adaptive fashion, the predictive model provides highly reliable estimates of asymptomatic and undetected COVID-19 patients, both of which are key players in COVID-19 transmission. Our dynamic modeling approach can be applied widely and will provide a new fillip to infectious disease management strategies worldwide.


title: A simple ecological model captures the transmission pattern of the coronavirus COVID-19 outbreak in China

text: The rapid spread of the 2019 novel coronavirus (COVID-19), initially reported in the city of Wuhan in China, and quickly transmitted to the entire nation and beyond, has become an international public health emergency. Estimating the final number of infection cases and the turning point (time with the fastest spreading rate) is crucial to assessing and improving the national and international control measures currently being applied. In this paper we develop a simple model based on infectious growth with a time-varying infection rate, and estimate the final number of infections and the turning point using data updated daily from 3 February 2020, when China escalated its initial public health measures, to 10 February. Our model provides an extremely good fit to the existing data and therefore a reasonable estimate of the time-varying infection rate that has largely captured the transmission pattern of this epidemic outbreak. Our estimation suggests that (i) the final number of infections in China could reach 78,000 with an upper 95% confidence limit of 88,880; (ii) the turning point of the fastest spread was on the 4th or the 5th of February; and (iii) the projected period for the end of the outbreak (i.e., when 95% of the final predicted number of infection is reached) will be the 24th of February, with an upper 95% confidence limit on the 19th of March. This suggests that the current control measures in China are excellent, and more than sufficient to contain the spread of this highly infectious novel coronavirus, and that the application of such measures could be considered internationally for the global control of this outbreak.


title: A Human-Pathogen SEIR-P Model for COVID-19 Outbreak under different intervention scenarios in Kenya

text: This work describes the mathematical modelling and dynamics of a novel Coronavirus disease 2019 (COVID-19) in Kenya. The mathematical model assumes Human-Human infection as well as Human-Pathogen interaction. Using the SEIR (Susceptible-Exposed-Infected-Recovered) compartmental model with additional component of the pathogen,we simulated the dynamics of COVID-19 outbreak and impact of different control measures. The resulting system of ordinary differential equations (ODEs) are directly solved using a combination of fourth and fifth-order Runge-Kutta methods. Simulation results indicate that non-pharmaceutical measures such as school closure, social distancing and movement restriction emphatically flatten the epidemic peak curve hence leading to a smaller number of overall disease cases.


title: Rapid implementation of mobile technology for real-time epidemiology of COVID-19

text: The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic (COVID-19) presents challenges to the robust collection of population-scale data to address this global health crisis. We established the COronavirus Pandemic Epidemiology (COPE) consortium to bring together scientists with expertise in big data research and epidemiology to develop a COVID-19 Symptom Tracker mobile application that we launched in the UK on March 24, 2020 and the US on March 29, 2020 garnering more than 2.25 million users to date. This mobile application offers data on risk factors, herald symptoms, clinical outcomes, and geographical hot spots. This initiative offers critical proof-of-concept for the repurposing of existing approaches to enable rapidly scalable epidemiologic data collection and analysis which is critical for a data-driven response to this public health challenge.


title: ASSESSING THE ROLE OF ZINC IN COVID-19 INFECTIONS AND MORTALITY: IS ZINC DEFICIENCY A RISK FACTOR FOR COVID-19?

text: Variables responsible for the differential COVID-19 pandemic severity among countries remain undefined. Zinc, a micronutrient required for immunocompetence, is found deficient in populations. We hypothesized the differential COVID-19 severity observed among European countries could be associated with the Zn-deficiency prevalence. The COVID-19 data from different stages of pandemic i.e., 8 April, 12 and 26 May 2020, were analyzed for covariation with the estimated Zn-deficiency. A significant, relatively stable, but negative correlation of Zn-deficiency with cases per million for the time period (r(20): -0.4930 to -0.5335, p-value: 0.02720 to 0.0154) and a steady improvement of covariation with deaths per million (r(20): -0.4056; p-value: 0.0760 on 26 May 2020) was observed. Considering, Zinc 's key immunomodulatory role, widespread deficiency along with the self- and prescribed intervention in different target groups, e.g. children, women, elderly, carefully planned dedicated exploratory studies to understand the basis of the observed association are advisable.