title: Transmission characteristics of the COVID-19 outbreak in China: a study driven by data

text: The COVID-19 outbreak has been a serious public health threat worldwide. We use individually documented case descriptions of COVID-19 from China (excluding Hubei Province) to estimate the distributions of the generation time, incubation period, and periods from symptom onset to isolation and to diagnosis. The recommended 14-day quarantine period may lead to a 6.7% failure for quarantine. We recommend a 22-day quarantine period. The mean generation time is 3.3 days and the mean incubation period is 7.2 days. It took 3.7 days to isolate and 6.6 days to diagnose a patient after his/her symptom onset. Patients may become infectious on average 3.9 days before showing major symptoms. This makes contact tracing and quarantine ineffective. The basic reproduction number is estimated to be 1.54 with contact tracing, quarantine and isolation, mostly driven by super spreaders.


title: Reflection and Recovery from Psychosis during the Time of COVID-19: Adaptation in Psychotherapy in the United States/ La reflexión y la recuperación de la psicosis durante el COVID-19: adaptación en la psicoterapia de EE UU

text: ABSTRACT In response to the coronavirus (COVID-19) pandemic several adaptations have allowed us to continue to provide one form of recovery-oriented psychotherapy to persons with psychosis: Metacognitive Insight and Reflection Therapy (MERIT) These successful adaptations have included the incorporation of patients' experience of the pandemic and the exploration of challenges from temporary changes in therapy platforms to deepen reflections about patients' self-experience, their experience of intersubjectivity and their own agentic responses to psychosocial challenges


Romantic Love in the Age of COVID-19


Trendbericht Analytische Chemie


Expert consensus on clinical management of patients with emergent high-risk cardiovascular disease during the epidemic period of coronavirus disease 2019 in military hospitals/ 2019冠状病毒肺炎疫情期间军队医院心血管急危重症患者 临床管理原则专家共识


title: A simulation-based procedure to estimate base rates from Covid-19 antibody test results I: Deterministic test reliabilities

text: We design a procedure (the complete Python code may be obtained at: https://github.com/abhishta91/antibody_montecarlo) using Monte Carlo (MC) simulation to establish the point estimators described below and confidence intervals for the base rate of occurrence of an attribute (e.g., antibodies against Covid-19) in an aggregate population (e.g., medical care workers) based on a test. The requirements for the procedure are the test's sample size (N) and total number of positives (X), and the data on test's reliability. The modus is the prior which generates the largest frequency of observations in the MC simulation with precisely the number of test positives (maximum-likelihood estimator). The median is the upper bound of the set of priors accounting for half of the total relevant observations in the MC simulation with numbers of positives identical to the test's number of positives. Our rather preliminary findings are: The median and the confidence intervals suffice universally; The estimator X/N may be outside of the two-sided 95% confidence interval; Conditions such that the modus, the median and another promising estimator which takes the reliability of the test into account, are quite close; Conditions such that the modus and the latter estimator must be regarded as logically inconsistent; Conditions inducing rankings among various estimators relevant for issues concerning over- or underestimation.


title: Protocol of a population-based prospective COVID-19 cohort study Munich, Germany (KoCo19)

text: Background: The SARS-CoV-2 pandemic is leading to the global introduction of public health interventions to prevent the spread of the virus and avoid the overload of health care systems, especially for the most severely affected patients. Scientific studies to date have focused primarily on describing the clinical course of patients, identifying treatment options and developing vaccines. In Germany, as in many other regions, current tests for SARS-CoV2 are not being conducted on a representative basis and in a longitudinal design. Furthermore, knowledge about the immune status of the population is lacking. Yet these data are needed to understand the dynamics of the pandemic and to thus appropriately design and evaluate interventions. For this purpose, we recently started a prospective population-based cohort in Munich, Germany, with the aim to better understand the state and dynamics of the pandemic. Methods: In 100, randomly selected constituencies out of 755, 3,000 Munich households are identified via random route and offered enrollment into the study. All household members are asked to complete a baseline questionnaire and subjects [≥]14 years of age are asked to provide a venous blood sample of [≤]3 ml for the determination of SARS-CoV-2 IgG/IgA status. The residual plasma and the blood pellet are preserved for later genetic and molecular biological investigations. For twelve months, each household member is asked to keep a diary of daily symptoms, whereabouts and contacts via WebApp. If symptoms suggestive for COVID-19 are reported, family members, including children <14 years, are offered a pharyngeal swab taken at the Division of Infectious Diseases and Tropical Medicine, LMU University Hospital Munich, for molecular testing for SARS-CoV-2. In case of severe symptoms, participants will be transferred to a Munich hospital. For one year, the study teams re-visits the households for blood sampling every six weeks. Discussion: With the planned study we will establish a reliable epidemiological tool to improve the understanding of the spread of SARS-CoV-2 and to better assess the effectiveness of public health measures as well as their socio-economic effects. This will support policy makers in managing the epidemic based on scientific evidence.


title: Visualization of the HIV-1 Env Glycan Shield Across Scales

text: The dense array of N-linked glycans on the HIV-1 Envelope Glycoprotein (Env), known as the “glycan shield”, is a key determinant of immunogenicity, yet intrinsic heterogeneity confounds typical structure-function analysis. Here we present an integrated approach of single-particle electron cryomicroscopy (cryo-EM), computational modeling, and site-specific mass-spectrometry (MS) to probe glycan shield structure and behavior at multiple levels. We found that dynamics lead to an extensive network of inter-glycan interactions that drive the formation of higher-order structure within the glycan shield. This structure defines diffuse boundaries between buried and exposed protein surface and creates a mapping of potentially immunogenic sites on Env. Analysis of Env expressed in different cell lines revealed how cryo-EM can detect subtle changes in glycan occupancy, composition, and dynamics that impact glycan shield structure and epitope accessibility. Importantly, this identified unforeseen changes in the glycan shield of Env obtained from expression in the same CHO cell line used for GMP production. Finally, by capturing the enzymatic deglycosylation of Env in a time-resolved manner we found that highly connected glycan clusters are resistant to digestion and help stabilize the pre-fusion trimer, suggesting the glycan shield may function beyond immune evasion. Significance Statement The HIV-1 Env “glycan shield” masks the surface of the protein from immune recognition, yet intrinsic heterogeneity defies a typical structure-function description. Using a complementary approach of cryo-EM, computational modeling, and mass-spectrometry we show how heterogeneity and dynamics affect glycan shield structure across scales. Our combined approach facilitated the development of new cryo-EM data analysis methods and allowed for validation of models against experiment. Comparison of Env across a range of glycosylation states revealed how subtle differences in composition impact glycan shield structure and affect the accessibility of epitopes on the surface. Finally, time-resolved cryo-EM experiments uncovered how highly connected glycan clusters help stabilize the pre-fusion trimer, suggesting the glycan shield may function beyond immune evasion.


title: A High-Coverage SARS-CoV-2 Genome Sequence Acquired by Target Capture Sequencing

text: This manuscript is based on the method we developed urgently to deal with the research requirement in the conflict between achieving a complete genome sequence for the evolutionary history of SARS-CoV-2 study and the low viral RNA concentration. Here, in this manuscript, we developed a set of SARS-CoV-2 enrichment probes to increase the sensitivity of sequence-based virus detection and characterization via obtaining the comprehensive genome sequence. Following the CDC health and safety guidelines, we test the concept using the culturing supernatant contain SARS-CoV-2 particles, and its full-length sequence was used for further analysis. The fraction of SARS-CoV-2 endogenous DNA was 93.47% with Cluster Factor about 1.1, which demonstrate that the numbers of mapped reads to SARS-CoV-2 reference sequence significantly increased, compared to metagenomic sequencing technology, following SARS-CoV-2 probe enrichment. Moreover, based on the high-quality sequence, we discussed the heterozygosity and viral expression during replication of coronavirus, and its phylogenetic relationship with other selected high-quality samples from The Genome Variation Map (GVM) (on 2020/03/22). We believe this manuscript is valuable for all the researchers who are interested in using clinical warp samples to obtain the high coverage of SARS-CoV-2 genome sequence with a relatively low concentration of viral particles. This would allow the clinician to correlate the diagnostic data with molecular monitoring in viral evolutional, the most importantly, to track the functional mutation of SARS-CoV-2.


title: Inflammation Level Severity and Death in Patients With COVID-19: A Rapid Systematic Review and Meta-Analysis

text: Background: An association among the use of angiotensin-converting-enzyme(ACE) inhibitors and angiotensin-receptor blockers(ARBs) with the clinical outcomes of coronavirus disease 2019 (COVID-19) is unclear. Methods: PubMed, EMBASE, and the preprint databases MedRxiv and BioRxiv were searched for relevant studies that assessed the association among inflammation level, application of ACEI/ARB, infection severity and death in patients with COVID-19. Odd risks(OR) and 95% confidence interval (CI) were combined using random-effects or fixed models depending on heterogeneity. Results: Eleven studies were included with a total of 33,483 patients. Our review showed ACEI/ARB therapy might be associated with the reduced inflammatory factor (interleukin-6) and elevated level of immune cells(CD3, CD8). Meta-analysis showed no significant increase in the risk of COVID-19 infection(OR:0.95, 95%CI:0.89-1.05) in patients receiving ACEI/ARB therapy, and ACEI/ARB therapy was associated with a decreased risk of severe COVID-19 (OR:0.75, 95%CI: 0.59-0.96) and mortality (OR:0.52, 95%CI: 0.35-0.79). Subgroup analyses showed that, among the general population, application of ACEI/ARB therapy was associated with reduced risks of all-cause death(OR:0.31, 95%CI: 0.13-0.75), and the risk of severe COVID-19(OR:0.79, 95%CI: 0.60-1.05) infection and COVID-19 infection(OR:0.85, 95% CI: 0.66-1.08) were not increased. Among patients with hypertension, the use of an ACEI/ARB was associated with a lower severity of COVID-19(OR:0.73, 95%CI: 0.51-1.03) and lower mortality(OR:0.57, 95%CI: 0.37-0.87), without evidence of an increased risk of COVID-19 infection(OR:1.00, 95%CI: 0.90-1.12). Conclusion: On the basis of the available evidence, this is the first meta-analysis showed that, in general population, the use of ACEI/ARB therapy was safe without an increased risk of COVID-19 infection and with a decreasing trend of severe COVID-19 infection and lower mortality. In patients with hypertension, the use of ACEI/ARB therapy should be encouraged, without increased risk of COVID-19 inflection, and better prognosis (a decreasing trends of severe COVID-19 and reduced all-cause death). Overall, ACEI/ARB therapy should be continued in patients who are at risk for, or have COVID-19, either in general population or hypertension patients. Our results need to be interpreted with caution considering the potential for residual confounders, and more well-designed studies that control the clinical confounders are necessary to confirm our findings. Key Words COVID-19; ACEI/ARB; SARS-COV-2; pneumonia; infectious disease; lung, hypertension


title: COVID-19: Dying is Bad--Losing Life is Worse

text: Background: COVID-19 was the leading cause of death in the United States over the three-month period March through May 2020. Another perspective is COVID-19s toll in terms of years of life lost. We calculated years of life lost for COVID-19 and other leading causes of death over those three months in the US. We also predicted years of life lost for COVID-19 and ischemic heart diseases (which includes heart attacks) for March through August 2020. Methods: Years of life lost are the sum of differences between life expectancy at age of death and age at death. Average years of life lost, years of life lost divided by the number of deaths, were also calculated. We used the COVID-19 Projections Using Machine Learning model to predict years of life lost from COVID-19 through the end of August 2020. Results: COVID-19 caused 12,035 more deaths than ischemic heart diseases during March through May 2020 but ischemic heart diseases years of life lost were 1.5% greater than those for COVID-19. Average years of life lost were 10.8 and 12.4 for COVID-19 and ischemic heart diseases, respectively. At the end of August, COVID-19 may overtake ischemic heart diseases as the leading cause of deaths and years of life lost in the US. Conclusion: Each COVID-19 death causes more than a decade of lost life in the US. We are reminded of a Danish Proverb that states "Prediction is difficult, especially when dealing with the future." We suggest that while dying is bad, losing life is even worse.


title: Geo-social gradients in predicted COVID-19 prevalence and severity in Great Britain: results from 2,266,235 users of the COVID-19 Symptoms Tracker app

text: Understanding the geographical distribution of COVID-19 through the general population is key to the provision of adequate healthcare services. Using self-reported data from 2,266,235 unique GB users of the COVID Symptom Tracker app, we find that COVID-19 prevalence and severity became rapidly distributed across the UK within a month of the WHO declaration of the pandemic, with significant evidence of urban hot-spots. We found a geo-social gradient associated with disease severity and prevalence suggesting resources should focus on urban areas and areas of higher deprivation. Our results demonstrate use of self-reported data to inform public health policy and resource allocation.


title: Identifying Therapeutic Compounds Targeting RNA-Dependent-RNA-Polymerase of Sars-Cov-2

text: pCOVID-19 emerged as the biggest threat of this century for mankind and later it spread across the globe through human to human transmission Scientists rushed to understand the structure and mechanism of the virus so that antiviral drugs or vaccines to control this disease can be developed A key to stop the progression of the disease is to inhibit the replication mechanism of Sars-Cov-2 RNA-dependent-RNA polymerase protein also called RdRp protein is the engine of Sars-Cov-2 that replicates the virus using viral RNA when it gains entry into the human cell Numerous drugs proposed for the treatment of COVID-19 such as Camostat Mesylate, Remdesivir, Famotidine, Hesperidin, etc are under trial to analyze the aftermath of their medicinal use Nature is enriched with compounds that have antiviral activities and can potentially play a pivotal role to inhibit this virus This study focuses on the phytochemicals that have the potential to exhibit antiviral activities A large number of compounds were screened and a cohort of most suitable ones are suggested via in-silico techniques which are used worldwide for drug discovery such as docking, binding analysis, Universal Force Field Analysis, Broyden-Fletcher-Goldfarb-Shanno (BFGS) Method, Molecular Dynamic Simulation, and Electrostatic Potential Calculation The proposed compounds are naturally occurring substances with low toxicity, very few side effects, proven anti-pathogenic effects, and most importantly are easily available /p


docid: jrwdhmst

title: Cirrhosis and COVID-19: a fatal case of viral peritonitis and disseminated infection

text: Pathogenesis and clinical presentation of Coronavirus Disease-19 outside the respiratory tract remain to be understood, especially in the immunocompromised. We report an unique case of cirrhosis decompensation with ascites and unprecedented evidence of SARS Coronavirus-2 peritonitis and disseminated infection, demonstrated by viral RNA detection in peritoneal fluid, as well as in blood serum, nasopharyngeal and stool specimens.


title: Ozone therapy for patients with SARS-COV-2 pneumonia: a single-center prospective cohort study

text: Importance Aside from supportive management, there remains no specific treatment for Coronavirus Disease 2019 (COVID-19). Objective: Determine whether ozonated autohemotherapy is associated with a shorter time to clinical improvement in patients with severe COVID-19 pneumonia. Design: Single-center proof-of-concept prospective cohort study. Setting: Internal Medicine ward at Policlinica Ibiza Hospital, Spain. Participants: Eighteen consecutive patients with laboratory confirmed COVID-19 infection and severe pneumonia who were admitted to hospital between 20th March and 19th April 2020. Exposures: Patients in the ozonated autohemotherapy arm received hemotherapy twice daily starting on the day of admission for a median of 4 days. Each treatment involved administration of 200 mL autologous whole blood enriched with 200 mL of oxygen-ozone mixture with a 40 g/mL ozone concentration. Patients in the control arm received supportive care. Assignment to hemotherapy versus usual care was determined based on the admitting physician on the day of admission, with only one of the three possible physicians prescribing ozonated autohemotherapy Main Outcomes: The primary outcome was time from hospital admission to clinical improvement, which was defined as either hospital discharge or a two-point improvement in clinical status measured on a six-point ordinal scale. Secondary outcomes were clinical improvement measured on the 7th, 14th and 28th day after admission, as well as time to a 2-fold reduction in concentrations of C-protein reactive, ferritin, D-dimer and lactate dehydrogenase. Results: The mean age of the cohort was 68 y and 72% (n=13) were male. Nine patients (50%) received ozonated autohemotherapy beginning on the day of admission. In unadjusted comparisons, ozonated autohemotherapy was associated with significantly shorter time to clinical improvement (median [IQR]), 7 days [6-10] vs 28 days [8-31], p=0.04) and significantly higher proportion of patients achieving 14-day clinical improvement (88.8% vs 33.3%, p=0.01). In risk-adjusted analyses, ozonated autohemotherapy was associated with a shorter mean time to clinical improvement (-11.3 days, p=0.04, 95% CI -22.25 to -0.42). Conclusions and Relevance: Ozonated autohemotherapy was associated with a significantly shorter time to clinical improvement in this prospective cohort study. Given the small sample size and single-center study design, these observations require evaluation in larger randomized controlled trials.


title: Agent-Level Pandemic Simulation (ALPS) for Analyzing Effects of Lockdown Measures

text: This paper develops an agent-level simulation model, termed ALPS, for simulating the spread of an infectious disease in a confined community. The mechanism of transmission is agent-to-agent contact, using parameters reported for Corona COVID-19 pandemic. The main goal of the ALPS simulation is analyze effects of preventive measures -- imposition and lifting of lockdown norms -- on the rates of infections, fatalities and recoveries. The model assumptions and choices represent a balance between competing demands of being realistic and being efficient for real-time inferences. The model provides quantification of gains in reducing casualties by imposition and maintenance of restrictive measures in place.


title: Association of Sickle Cell Trait with Risk and Mortality of COVID-19: Results from the UK Biobank

text: We tested the hypothesis that patients with sickle cell trait (SCT), a common condition in individuals of African descent, have increased risk and mortality for coronavirus disease (COVID-19) in the UK Biobank. By June 17, 2020, 1,550 of 7,668 (20%) tested subjects were positive for COVID-19, including 298 (19%) deaths. Blacks had higher rates than Whites for COVID-19 infections (79/222=36% vs. 1,342/7,010=19%, P=1.28x10-9). Among Blacks, SCT carriers did not have higher infection rates (5/15=33%) than non-SCT carriers (74/207=36%), P=1.00. However, SCT carriers had a trend of higher death rates (2/5=40%) than non-SCT carriers (12/74=16%), although not statistically significant (P=0.21).


title: Cytokine storm and colchicine potential role in fighting SARS-CoV-2 pneumonia

text: For some patients with SARS-CoV-2, the worst clinical damage is not caused by the virus itself, but by an overactive inflammatory state In fact, in some people the immune system goes into overdrive and launches a large-scale assault on the tissue known as cytokine storm This excessive inflammatory/immune reaction can damage tissue and eventually kill people Evidence shows that blocking such cytokine storms can be effective and trials are under way to test drugs that act by reducing cytokine response, such as tocilizumab and sarilumab which bind interleukin 6 (IL-6), or anakinra which is the interleukin 1 receptor antagonist (IL-1) However, other drugs that block the cytokine cascade can also be considered In this article we describe the scientific and molecular motivation for the use of drugs that act by modulating the hyperactive inflammatory system in severe patients suffering from SARS-CoV-2, considering in particular an old drug that has been in use for many years for other therapeutic indications such as colchicine, and that could be favorable to its use, with low cost and good tolerability


title: Structural and Functional Implications of Spike Protein Mutational Landscape in SARS-CoV-2

text: SARS-CoV-2, the causative agent of COVID-19 pandemic, is an RNA virus prone to mutations. Interaction of SARS-CoV-2 Spike (S) protein with the host cell receptor, Angiotensin-I Converting Enzyme 2 (ACE2) is pivotal for attachment and entry of the virus. Yet, natural mutations acquired on S protein during the pandemic and their impact on viral infectivity, transmission dynamics and disease pathogenesis remains poorly understood. Here, we analysed 2952 SARS-CoV-2 genomes across the globe, and identified a total of 1815 non-synonymous mutations in the S-protein that fall into 54 different types. We observed that six of these distinct mutations were located in the Receptor Binding Domain (RBD) region that directly engages host ACE2. Molecular phylogenetic analysis revealed that these RBD mutations cluster into distinct phyletic clades among global subtypes of SARS-CoV-2 implying possible emergence of novel sublineages of the strain. Structure-guided homology modelling and docking analysis predicted key molecular rearrangements in the ACE2 binding interface of RBD mutants that could result in altered virus-host interactions. We propose that our findings could be significant in understanding disease dynamics and in developing vaccines, antibodies and therapeutics for COVID-19. Importance COVID-19 pandemic shows considerable variations in disease transmission and pathogenesis globally, yet reasons remain unknown. Our study identifies key S-protein mutations prevailing in SARS-CoV-2 strain that could alter viral attachment and infectivity. We propose that the interplay of these mutations could be one of the factors driving global variations in COVID-19 spread. In addition, the mutations identified in this study could be an important indicator in predicting efficacies of vaccines, antibodies and therapeutics that target SARS-CoV-2 RBD-ACE2 interface.


docid: dyzinmmm

title: Investigating spatiotemporal patterns of the COVID-19 in Sao Paulo State, Brazil

text: As of May 16th, 2020, the number of confirmed cases and deaths in Brazil due to COVID-19 hit 233,142 and 15,633, respectively, making the country one of the most affected by the pandemic. The State of Sao Paulo (SSP) hosts the largest number of confirmed cases in Brazil, with over 60,000 cases to date. Here we investigate the spatial distribution and spreading patterns of COVID-19 in the SSP by mapping the spatial autocorrelation and the clustering patterns of the virus in relation to the population density and the number of hospital beds. Moran's I and LISA clustering analysis indicated that Sao Paulo City is a significant hotspot for both the confirmed cases and deaths, whereas other cities across the State could be considered colder spots. Bivariate Moran's I also showed that the population density is a key indicator for the number of deaths, whereas the number of hospital beds is less related, implying that the fatality depends substantially on the actual patient's condition. Social isolation measures throughout the SSP have been gradually increasing since early March, an action that helped to slow down the emergence of the new confirmed cases, highlighting the importance of the safe-distancing measures in mitigating the local transmission within and between cities in the SSP.


title: Clinical Management and Mortality among COVID-19 Cases in Sub-Saharan Africa: A retrospective study from Burkina Faso and simulated case data analysis

text: Background: Absolute numbers of COVID-19 cases and deaths reported to date in the sub-Saharan Africa (SSA) region have been significantly lower than those across the Americas, Asia, and Europe. As a result, there has been limited information about the demographic and clinical characteristics of deceased cases in the region, as well as the impacts of different case management strategies. Methods: Data from deceased cases reported across SSA through May 10, 2020 and from hospitalized cases in Burkina Faso through April 15, 2020 were analyzed. Demographic, epidemiological, and clinical information on deceased cases in SSA was derived through a line-list of publicly available information and, for cases in Burkina Faso, from aggregate records at the Center Hospitalier Universitaire de Tengandogo in Ouagadougou. A synthetic case population was derived probabilistically using distributions of age, sex, and underlying conditions from populations of West African countries to assess individual risk factors and treatment effect sizes. Logistic regression analysis was conducted to evaluate the adjusted odds of survival for patients receiving oxygen therapy or convalescent plasma, based on therapeutic effectiveness observed for other respiratory illnesses. Results: Across SSA, deceased cases for which demographic data are available have been predominantly male (63/103, 61.2%) and over 50 years of age (59/75, 78.7%). In Burkina Faso, specifically, the majority of deceased cases either did not seek care at all or were hospitalized for a single day (59.4%, 19/32); hypertension and diabetes were often reported as underlying conditions. After adjustment for sex, age, and underlying conditions in the synthetic case population, the odds of mortality for cases not receiving oxygen therapy was significantly higher than those receiving oxygen, such as due to disruptions to standard care (OR: 2.07; 95% CI: 1.56-2.75). Cases receiving convalescent plasma had 50% reduced odds of mortality than those who did not (95% CI: 0.24-0.93). Conclusion: Investment in sustainable production and maintenance of supplies for oxygen therapy, along with messaging around early and appropriate use for healthcare providers, caregivers, and patients could reduce COVID-19 deaths in SSA. Further investigation into convalescent plasma is warranted, as data on its effectiveness specifically in treating COVID-19 becomes available. The success of supportive or curative clinical interventions will depend on earlier treatment seeking, such that community engagement and risk communication will be critical components of the response.


先端的研究設備の導入・更新における研究力分析の活用


title: Individuals with autism have no detectable deficit in neural markers of prediction error when presented with auditory rhythms of varied temporal complexity

text: The brain’s ability to encode temporal patterns and predict upcoming events is critical for speech perception and other aspects of social communication. Deficits in predictive coding may contribute to difficulties with social communication and overreliance on repetitive predictable environments in individuals with autism spectrum disorder (ASD). Using a mismatch negativity (MMN) task involving rhythmic tone sequences of varying complexity, we tested the hypotheses that 1) individuals with ASD have reduced MMN response to auditory stimuli that deviate in presentation timing from expected patterns, particularly as pattern complexity increases and 2) amplitude of MMN signal is inversely correlated with level of impairment in social communication and repetitive behaviors. Electroencephalography was acquired as individuals (age 6-21years) listened to repeated five-rhythm tones that varied in the Shannon entropy of the rhythm across three conditions (zero, medium-1 bit) and high-2 bit entropy). The majority of the tones conformed to the established rhythm (standard tones); occasionally the 4th tone was temporally shifted relative to its expected time of occurrence (deviant tones). Social communication and repetitive behaviors were measured using the Social Responsiveness Scale and Repetitive Behavior Scale-Revised. Both neurotypical controls (n=19) and individuals with ASD (n=21) show stepwise decreases in MMN as a function of increasing entropy. Contrary to the result forecasted by a predictive coding hypothesis, individuals with ASD do not differ from controls in these neural mechanisms of prediction error to auditory rhythms of varied temporal complexity, and there is no relationship between these signals and social communication or repetitive behavior measures. Lay Summary We tested the idea that the brain’s ability to use previous experience to influence processing of sounds is weaker in individuals with autism spectrum disorder (ASD) than in neurotypical individuals. We found no difference between individuals with ASD and neurotypical controls in brain wave responses to sounds that occurred earlier than expected in either simple or complex rhythms. There was also no relationship between these brain waves and social communication or repetitive behavior scores.


title: Analytical sensibility and specificity of two RT-qPCR protocols for SARS-CoV-2 detection performed in an automated workflow

text: The World Health Organization declared that COVID-19 outbreak constituted a Public Health Emergency of International Concern and the development of reliable laboratory diagnosis of SARS-CoV-2 became mandatory to identify, isolate and provide optimized care for patients early. RT-qPCR testing of respiratory secretions is routinely used to detect causative viruses in acute respiratory infection. RT-qPCR in-house protocols to detect the SARS-CoV-2 have been described. Validations of these protocols are considered a key knowledge gap for COVID-19, especially if executed in a high throughput format. Here, we investigate the analytical sensitivity and specificity of two interim RT-qPCR protocols for the qualitative detection of SARS-CoV-2 executed in a fully automated platform. Under our conditions, the N1 and RdRP (modified) showed the highest analytical sensitivity for their RNA targets. E assay, in its original concentration, was considered a tertiary confirmatory assay. Taken together, N1, RdRP (optimized) and E presented appropriated analytical sensibility and specificity in our automated RT-qPCR workflow for COVID-19 virus, E being at least 4-fold less sensitive than the others. This study highlights the importance of local validation of in-house assays before its availability to the population. The use of the synthetic RT-qPCR target to investigate novel assays diagnostic parameters in automated workflows is a quick, simple effective way to be prepared for upcoming threats. The proposed assay detected the first SARS-CoV-2 infection in Brazilian Central-West.


Post COVID-19 lesson: Understand the environment for human survival and sustenance


title: Performance characteristics of a high throughput automated transcription mediated amplification test for SARS-CoV-2 detection

text: The COVID19 pandemic caused by the new SARSCoV2 coronavirus has imposed severe challenges on laboratories in their effort to achieve sufficient diagnostic testing capability for identifying infected individuals. In this study we report the analytical and clinical performance characteristics of a new, high throughput, fully automated nucleic acid amplification test system for the detection of SARSCoV2. The assay utilizes target capture, transcription mediated amplification, and acridinium ester labeled probe chemistry on the automated Panther System to directly amplify and detect two separate target sequences in the ORF1ab region of the SARSCoV2 RNA genome. The probit 95% limit of detection of the assay was determined to be 0.004 TCID50/ml using inactivated virus, and 25 c/ml using synthetic in vitro transcript RNA targets. Analytical sensitivity (100% detection) was confirmed to be 83 to 194 c/ml using three commercially available SARSCoV2 nucleic acid controls. No cross reactivity or interference was observed with testing six related human coronaviruses, as well as 24 other viral, fungal, and bacterial pathogens, at high titer. Clinical nasopharyngeal swab specimen testing (N=140) showed 100%, 98.7%, and 99.3% positive, negative, and overall agreement, respectively, with a validated reverse transcription PCR NAAT for SARSCoV2 RNA. These results provide validation evidence for a sensitive and specific method for pandemic-scale automated molecular diagnostic testing for SARSCoV2.


title: An improved mathematical prediction of the time evolution of the Covid-19 Pandemic in Italy, with Monte Carlo simulations and error analyses

text: Here we present an improved mathematical analysis of the time evolution of the Covid-19 pandemic in Italy and a statistical error analyses of its evolution, including Monte Carlo simulations with a very large number of runs to evaluate the uncertainties in its evolution. A previous analysis was based on the assumption that the number of nasopharyngeal swabs would be constant, however the number of daily swabs has been increasing with an average factor of about five with respect to our previous analysis. Therefore, here we consider the time evolution of the ratio of the diagnosed positive cases to number of swabs, which is more representative of the evolution of the pandemic when the number of swabs is increasing or changing in time. We consider a number of possible distributions representing the evolution of the pandemic in Italy and we test their prediction capability over a period up to four weeks. The results show that a distribution of the type of Planck's black body radiation law provides very good forecasting. The use of different distributions provides an independent estimate of the uncertainty. We then consider five possible cases for the number of daily swabs and we then estimate the potential dates of a substantial reduction in the number of diagnosed positive cases. We then perform Monte Carlo simulations with 25000 runs to evaluate the uncertainty in the prediction of the date of a substantial reduction in the number of diagnosed daily cases. Finally, we present an alternative method to evaluate the uncertainty in our mathematical predictions based on the study of each region of Italy and we present an application of the Central Limit Theorem with 100000 runs to display the uncertainty in our mathematical predictions based on the analysis of each region.


title: Full-length genome sequence of segmented RNA virus from ticks was obtained using small RNA sequencing data

text: In 2014, A novel tick-borne virus of the genus Flavivirus was first reported from the Mogiana region in Brazil. This virus was named the Mogiana tick virus (MGTV). Later, MGTV was also named as Jingmen tick virus (JMTV), Kindia tick virus (KDTV), Guangxi tick virus (GXTV) etc. In the present study, we used small RNA sequencing (sRNA-seq) to detect viruses in ticks and detected MGTV in Amblyomma testudinarium ticks, which had been captured in Yunnan province of China in the year of 2016. The full-length genome sequence of a new MGTV strain Yunnan2016 (GenBank: MT080097, MT080098, MT080099 and MT080100) was obtained and recommended to be included into the NCBI RefSeq database for the future studies of MGTV. Our phylogenetic analyses showed that viruses named MGTV, JMTV, KDTV and GXTV are monophyletic: the MGTV group (lineage) of viruses. We show, for the first time, that 5′ and 3′ sRNAs can be used to obtain full-length sequences of the 5’ and 3’ ends of, but not limited to genome sequences of RNA viruses. And we proved the feasibility of using the sRNA-seq based method for the detection of viruses in a sample containing miniscule RNA.


title: Calcium channel blocker amlodipine besylate is associated with reduced case fatality rate of COVID-19 patients with hypertension

text: The coronavirus disease (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread to more than 100 countries posing as a serious threat to the public health on a global scale. Patients with comorbidity such as hypertension suffer more severe infection with elevated case fatality rate. Development of effective anti-viral drug is in urgent need to treat COVID-19 patients. Here we report that calcium channel blockers (CCBs), a type of anti-hypertension drugs that are widely used in the clinics, can significantly inhibit the post-entry replication events of SARS-CoV-2 in vitro. Comparison with two other major types of anti-hypertension drugs, the angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), showed that only CCBs display significant anti-SARS-CoV-2 efficacy. Combined treatment with chloroquine and CCBs significantly enhanced the anti-SARS-CoV-2 efficacy. Retrospective clinical investigation of COVID-19 patients revealed that the CCB amlodipine besylate administration distinctly reduced the case fatality rate of patients with hypertension. Results from this study suggest that CCB administration for COVID-19 patients with hypertension as the comorbidity might improve the disease outcome.


title: Heat inactivating and reusing of virus-contaminated disposable medical mask

text: As the prevalence of COVID-19 in all the area of China and continuous spread to many other countries, it is in urgent need of medical mask for community people. We have reported a simple method to inactivate artificially influenza virus-contaminated medical mask without affecting the filterability of mask by heating with hair dryer for 30min. In this study, we extended our studies to optimize our protocols and evaluate the filterability of mask after several-rounds of heat treatment. We found that baking at 70 for 30min almost completely inactivated virus as hair dryer treatment for 30min described before. One-round of heat treatment with hair dryer for 30min or baking at 70 for 30min did not affect filterability of mask whilst two-rounds of treatment slightly but significantly reduced filterability of mask. Thus, heating with hair dryer for 30min or baking at 70 for 30min can inactive contaminated medical mask and the treated mask can be reused at least once.


title: Management of Advanced Therapies in Parkinson's Disease Patients in Times of Humanitarian Crisis: The COVID-19 Experience.

text: Background Although the COVID-19 pandemic is affecting a relatively small proportion of the global population, its effects have already reached everyone. The pandemic has the potential to differentially disadvantage chronically ill patients, including those with Parkinson's disease (PD). The first health care reaction has been to limit access to clinics and neurology wards to preserve fragile patients with PD from being infected. In some regions, the shortage of medical staff has also forced movement disorders neurologists to provide care for patients with COVID-19. Objective To share the experience of various movement disorder neurologists operating in different world regions and provide a common approach to patients with PD, with a focus on those already on advanced therapies, which may serve as guidance in the current pandemic and for emergency situations that we may face in the future. Conclusion Most of us were unprepared to deal with this condition given that in many health care systems, telemedicine has been only marginally available or only limited to email or telephone contacts. In addition, to ensure sufficient access to intensive care unit beds, most elective procedures (including deep brain stimulation or the initiation of infusion therapies) have been postponed. We all hope there will soon be a time when we will return to more regular hospital schedules. However, we should consider this crisis as an opportunity to change our approach and encourage our hospitals and health care systems to facilitate the remote management of chronic neurological patients, including those with advanced PD.


title: Community engagement for COVID-19 prevention and control: A Rapid Evidence Synthesis

text: Introduction Community engagement has been considered a fundamental component of past outbreaks, such as Ebola. The COVID-19 pandemic and its control efforts require social actions and behaviours, all of which place a large reliance on individual and community compliance, highlighting the need for appropriate community engagement to support such work. However, there is concern over the lack of involvement of communities within COVID-19 thus far. Identifying how community engagement approaches have been used in past epidemics may support more robust implementation of community engagement within COVID-19 response. Methodology A rapid evidence review was conducted to identity how community engagement is used for infectious disease prevention and control during epidemics. Three databases (PubMed, CINHAL and Scopus) were searched in addition to extensive snowballing for grey literature. Previous epidemics were limited to Ebola, Zika, SARS, MERS and H1N1 since 2000. No restrictions were applied to study design or language, though articles must have detailed a minimum of one community engagement for infection prevention and control initiative. All authors participated in searching, screening, and data extraction, with a minimum of two authors at each stage. Results From 1,112 references identified in our search, 32 articles met our inclusion criteria. All but 3 articles were published on or after 2015 which details 37 community engagement initiatives for Ebola (n=28), Zika (n=5) and H1N1 (n=4). Twenty-seven of these initiatives were implemented in low-income countries and 10 from high-income countries. Six broad community engagement actors were identified: local leaders, community and faith-based organisations, community groups, health facility or community health committees, individuals and key stakeholders. These actors worked across six different functions: designing and planning, community entry and trust-building, social and behaviour change communication, risk communication, surveillance and tracing, and logistics and administration. Leaders were the most prevalent actor being engaged, and behaviour change communication, risk communication, and surveillance and tracing were the most common function of community engagement. Implementation considerations community engagement in prevention and control of COVID-19 are reported within. Conclusion COVID-19 global presence and social transmission pathways require social and community responses. This may be particularly important to reach marginalised populations and support equity-informed responses. Previous experience from outbreaks shows that community engagement can take many forms and include different actors and approaches who support various prevention and control activities. Countries worldwide are encouraged to assess existing community engagement structures, and utilise community engagement approaches to support contextually specific, acceptable and appropriate COVID-19 prevention and control measures.


title: Pulmonary contusion mimicking COVID-19: A case report

text: BACKGROUND: Coronavirus disease 2019 (COVID-19) is a major public health emergency with obvious characteristics of human-to-human transmission, and there are infective asymptomatic carriers. Early identification and proper management of patients with COVID-19 are important. Features in chest computed tomography (CT) can facilitate identifying newly infected individuals. However, CT findings of some lung contusions are similar to those of COVID-19, as shown in the present case. CASE SUMMARY: A 46-year-old woman was admitted to hospital for backache and foot pain caused by a fall injury 1 d before hospitalization. She was suspected of having COVID-19, since there was a confirmed COVID-19 case near her residence. But she had no fever, cough, chest tightness, difficult breathing, nausea, vomiting, or diarrhea, etc. On physical examination, the lower posterior chest of both sides showed dullness on percussion and moist rales at the end of inspiration on auscultation. The white blood cell count and lymphocyte count were 10.88 × 10(9)/L and 1.04 × 10(9)/L, respectively. CT performed on February 7, 2020 revealed that both lungs were scattered with patchy ground-glass opacity. The patient was diagnosed with pulmonary contusion with thoracic spinal fracture (T12), calcaneal fracture, and pelvic fracture. On day 9 after conservative treatment, her condition was alleviated. On review of the chest CT, the previous shadows were significantly reduced. CONCLUSION: Differential diagnosis of lung contusion and COVID-19 must be emphasized. Both conditions require effective prompt actions, especially COVID-19.


title: The Risk of Lifting COVID-19 Confinement in Mexico

text: The novel coronavirus SARS-CoV-2 has paralysed our societies, leading to self isolation and quarantine for several days. As the 10th most populated country in the world, Mexico is on a major threat by COVID-19 due to the limitations of intensive care capacities, and a total of about 1.5 hospital beds for every 1000 citizens. In this paper, we projected different scenarios to evaluate sharp or gradual quarantine lifting strategies, however, even in the hypothetical scenario that Mexico would continue with full confinement, hospitals would be reaching the maximum capacity of hospital bed occupancy. Mexican government is planning to relax the strict social distancing regulations on 1 June 2020, however, epidemic rebound risks are latent. Our results suggest that lifting social confinement needs to be gradually sparse while maintaining a decentralized region strategy among the Mexican states. To substantially lower the number of infections, predictions highlight that the elderly should remain in social confinement (approximately 11.3% of the population); the confined working class (roughly 27% of the population) must gradually return in at least four parts in consecutive months; and to the last the return of students to schools (about 21.7%). As the epidemic progresses, de-confinement strategies need to be continuously re-adjusting with the new pandemic data. Assuming the most optimistic scenario by our predictions, the smallest number of new COVID-19 cases, Mexico would require at least a 3 fold increase in hospital capacities dedicated for COVID-19. Furthermore, to observe the real dimension of the epidemic, Mexico would need to increase to at least 18 samples per 1000 people, currently is only 0.6 per 1000. All mathematical models, including ours, are only a possibility of many of the future, however, the different scenarios that were developed here highlight that a gradual decentralized region de-confinement with a significant increase in healthcare capacities is paramount to avoid a high death toll in Mexico.


title: Prediction of the time evolution of the COVID-19 disease in Guadeloupe with a stochastic evolutionary model

text: Predictions on the time-evolution of the number of severe and critical cases of COVID-19 patients in Guadeloupe are presented. A stochastic model is purposely developed to explicitly account for the entire population (≈ 400000 inhabitants) of Guadeloupe. The available data for Guadeloupe are analysed and combined with general characteristics of the COVID-19 to constrain the parameters of the model. The time-evolution of the number of cases follows the well-known exponential-like model observed at the very beginning of a pandemic outbreak. The exponential growth of the number of infected individuals is controlled by the so-called basic reproductive number, R0, defined as the likely number of additional cases generated by a single infectious case during its infectious period TI. Because of the rather long duration of infectious period (≈ 14 days) a high rate of contamination is sustained during several weeks after the beginning of the containment period. This may constitute a source of discouragement for people restrained to respect strict containment rules. It is then unlikely that, during the containment period, R0 falls to zero. Fortunately, our models shows that the containment effects are not much sensitive to the exact value of R0 provided we have R0 < 0.6. For such conditions, we show that the number of severe and critical cases is highly tempered about 4 to 6 weeks after the beginning of the containment. Also, the maximum number of critical cases (i.e. the cases that may exceed the hospital intensive care capacity) remains near 30 when R0 < 0.6. For a larger R0 = 0.8 a slower decrease of the number of critical cases occurs, leading to a larger number of deceased patients. This last example illustrates the great importance to maintain an as low as possible R0 during and after the containment period. The rather long delay between the beginning of the containment and the appearance of the slowing-down of the rate of contamination puts a particular strength on the communication and sanitary education of people. To be mostly efficient, this communication must be done by a locally recognised medical staff. We believe that this point is a crucial matter of success.


title: Evaluation of effects of public health interventions on COVID-19 transmission for Pakistan: A mathematical simulation study

text: Background: In an effort to contain the COVID-19 epidemic, many governments across the world have enforced lockdown or social distancing measures. Several outbreak models have been developed to investigate the effects of different public health strategies for COVID-19, but they have not been developed for Pakistan and other South East Asian countries, where a large proportion of global population resides. Methods: We developed a stochastic individual contact model by extending the widely-used Susceptible-Infectious-Recovered (SIR) compartment model with additional compartments to model both anticipated mitigating effects of public health intervention strategies for Pakistan. We estimated the projected spread, number of hospitalizations, and case fatalities under no intervention and four increasingly stringent public health strategies of social distancing and self-isolation at the national and provincial levels of Pakistan. Results: Our analysis shows that without any public health interventions the expected number of cumulative case fatalities is 671,596 in Pakistan with the virus is expected to peak in terms of the number of required ICU-hospitalizations at 198,593 persons by the end of the June 2020. The estimated total numbers of cumulative case fatalities are lower for other public health strategies with strict social distancing showing the lowest number of deaths at 1,588 (Self-isolation: n=341,359; Flexible social distancing strategy: n=3,995; and Exit strategy: n=28,214). The lowest number of required ICU-hospitalization is also estimated for strict social distancing strategy (n=266 persons at the end of May 2020). Generally, the simulated effects of the different public health strategies at the provincial-level were similar to the national-level with strict social distancing showing the fewest number of case fatalities and ICU-hospitalizations. Conclusion: Our results indicate that case fatalities and ICU-hospitalizations for Pakistan will be high without any public health interventions. While strict social distancing can potentially prevent a large number of deaths and ICU-hospitalizations, the government faces an important dilemma of potentially severe economic downfall. Consideration of a temporary strict social distancing strategy with gradual return of the lower-risk Pakistani population, as simulated in our exit strategy scenario, may an effective compromise between public health and economy of Pakistani population.


title: Objective sensory testing methods reveal a higher prevalence of olfactory loss in COVID-19 positive patients compared to subjective methods: A systematic review and meta-analysis

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has currently infected over 6.5 million people worldwide. In response to the pandemic, numerous studies have tried to identify the causes and symptoms of the disease. Emerging evidence supports recently acquired anosmia (complete loss of smell) and hyposmia (partial loss of smell) as symptoms of COVID-19, but studies of olfactory dysfunction show a wide range of prevalence, from 5% to 98%. We undertook a search of Pubmed/Medline and Google Scholar with the keywords 'COVID-19', 'smell', and/or 'olfaction'. We included any study that quantified olfactory loss as a symptom of COVID%[minus]19. Studies were grouped and compared based on the type of method used to measure smell loss - subjective measures such as self-reported smell loss versus objective measures using rated stimuli - to determine if prevalence rate differed by method type. For each study, 95% confidence intervals (CIs) were calculated from point estimates of olfactory disturbance rates. We identified 34 articles quantifying anosmia as a symptom of COVID-19, collected from cases identified from January 16 to April 30, 2020. The pooled prevalence estimate of smell loss was 77% when assessed through objective measurements (95% CI of 61.4-89.2%) and 45% with subjective measurements (95% CI of 31.1-58.5%). Objective measures are a more sensitive method to identify smell loss as a result of infection with SARS-CoV-2. The use of subjective measures, while expedient during the early stages of the pandemic, underestimates the true prevalence of smell loss.


title: Machinability and Surface Integrity Characterization in Hard Turning of AISI 4320 Bearing Steel Using Different CBN Inserts

text: Abstract The thermomechanical interaction between the cutting tool and the workpiece in any material removal process is a key factor in defining the efficiency and productivity of the process. It is especially important in cutting hard-to-machine materials such as titanium- and nickel-based alloys or hardened steels. The productivity of the process can be defined in terms of machining time, intervals of tool change (due to tool wear) and surface integrity characteristics such as dimensional tolerances, surface roughness and the machining-affected zone. The objective of this work is to conduct a comprehensive study of the performance of three different industrial-grade CBN cutting inserts during hard turning of AISI 4320 case-carburized steel. The CBN inserts all had the same geometry but used different edge preparation and coating technologies. To quantify tool performance, the cutting forces and tool wear were measured at consistent intervals and the surface integrity of the workpiece was characterized in terms of surface roughness, white and dark layer depths, micro-hardness and residual stresses. Results show that the stability of the cutting edge on two of the tested inserts plays an important role in determining tool life (where 60% higher tool life was achieved compared to the other tested insert with unstable cutting edge), cutting force stability and the formation of compressive residual stresses on the surface of the turned workpiece


title: A HEURISTIC MODEL FOR SPREAD OF COVID-19 INFECTION CASES IN INDIA

text: A simple heuristic model for spread of COVID-19 infections in India is presented and compared with reported data up to April 10, 2020. Spread of infection is considered to be initiating from infected individuals and spread is assumed to take place in a compounding manner. Some of the data needed are taken from readily available sources in the web. The possible progress is then estimated based on model presented and possible scenarios are highlighted.


title: Risk of Transmission of infection to Healthcare Workers delivering Supportive Care for Coronavirus Pneumonia;A Rapid GRADE Review

text: Abstract Background: Avenues of treatment currently implemented for Covid-19 pandemic are largely supportive in nature. Non -availability of an effective antiviral treatment makes supportive care for acute hypoxic respiratory failure is the most crucial intervention. Highly contagious nature of Covid-19 had created stress and confusion among front line Health Care Workers (HCWs) regarding infectious risk of supportive interventions and best preventive strategies. Purpose: To analyze and summarize key evidence from published literature exploring the risk of transmission of Covid-19 related to common supportive care interventions in hospitalized patients and effectiveness of currently used preventive measures in hospital setting. Data Sources: Curated Covid-19 literature from NCBI Computational Biology Branch ,Embase and Ovid till May 20,2020.Longitudinal and reference search till June 28,2020 Study Selection: Studies pertaining to risk of infection to HCWs providing standard supportive care of hospitalized Covid-19 mainly focusing on respiratory support interventions.Indirect studies from SARS,MERS or other ARDS pathology caused by infectious agents based on reference tracking and snow ball search . Clinical, Healthy volunteer and mechanistic studies were included. Two authors independently screened studies for traditional respiratory supportive-care (Hypoxia management, ventilatory support and pulmonary toileting) related transmission of viral or bacterial pneumonia to HCWs. Data Extraction: Two authors (TK and SP) independently screened articles and verified for consensus. Quality of studies and level of evidence was assessed using Oxford Center for Evidence Based Medicine (OCEBM) , Newcastle - Ottawa quality assessment Scale for observational studies and Grading of Recommendations Assessment, Development and Evaluation (GRADE) system for grading evidence. Data Synthesis: 21 studies were eligible for inclusion. In 11 mechanistic studies, 7 were manikin based,1 was in the setting of GNB pneumonia ,2 were healthy volunteer study and 1 was heterogenous setting.Out of 10 clinical studies ,5 were case controlled and 6 were cohort studies. Risk of corona virus transmission was significantly high in HCWs performing or assisting endotracheal intubation or contact with respiratory secretion.(Moderate certainty evidence, GRADE B) Safety of nebulization treatment in corona virus pneumonia patients are questionable(Low certainty evidence, GRADE C).Very low certainty evidence exist for risk of transmission with conventional HFNC (GRADE D) and NIV (GRADE D),CPR (GRADE D),Bag and mask ventilation(GRADE D).Moderate certainty evidence exist for protective effect of wearing a multilayered mask, gown , eye protection and formal training for PPE use (GRADE B).Low certainty evidence exist for transmission risk with bag and mask ventilation, suctioning before and after intubation and prolonged exposure (GRADE C).Certainty of evidence for wearing gloves,post exposure hand washing and wearing N 95 mask is low(GRADE C). Limitations: This study was limited to articles with English abstract. Highly dynamic nature of body of literature related to Covid-19, frequent updates were necessary even during preparation of manuscript and longitudinal search was continued even after finalizing initial search. Due to the heterogeneity and broad nature of the search protocol, quantitative comparisons regarding the effectiveness of included management strategies could not be performed. Direct evidence was limited due to poor quality and non-comparative nature of available Covid-19 reporting. Conclusions: Major risk factors for transmission of corona virus infection were, performing or assisting endotracheal intubation and contact with respiratory secretion. Risk of transmission with HFNC or NIV can be significantly decreased by helmet interface, modified exhalation circuit or placing a properly fitting face mask over patient interface of HFNC. Evidence for risk of transmission with CPR, suctioning before or after intubation or bag and mask ventilation of very low certainty. Significant protective factors are Formal training for PPE use, consistently wearing mask, gown and eye protection. Primary Funding Source: None Disclosure: None of the authors have any conflict of interest to disclose.


title: Public Opinions towards COVID-19 in California and New York on Twitter

text: Background: With the pandemic of COVID-19 and the release of related policies, discussions about the COVID-19 are widespread online. Social media becomes a reliable source for understanding public opinions toward this virus outbreak. Objective: This study aims to explore public opinions toward COVID-19 on social media by comparing the differences in sentiment changes and discussed topics between California and New York in the United States. Methods: A dataset with COVID-19-related Twitter posts was collected from March 5, 2020 to April 2, 2020 using Twitter streaming API. After removing any posts unrelated to COVID-19, as well as posts that contain promotion and commercial information, two individual datasets were created based on the geolocation tags with tweets, one containing tweets from California state and the other from New York state. Sentiment analysis was conducted to obtain the sentiment score for each COVID-19 tweet. Topic modeling was applied to identify top topics related to COVID-19. Results: While the number of COVID-19 cases increased more rapidly in New York than in California in March 2020, the number of tweets posted has a similar trend over time in both states. COVID-19 tweets from California had more negative sentiment scores than New York. There were some fluctuations in sentiment scores in both states over time, which might correlate with the policy changes and the severity of COVID-19 pandemic. The topic modeling results showed that the popular topics in both California and New York states are similar, with "protective measures" as the most prevalent topic associated with COVID-19 in both states. Conclusions: Twitter users from California had more negative sentiment scores towards COVID-19 than Twitter users from New York. The prevalent topics about COVID-19 discussed in both states were similar with some slight differences.


title: The Role of Vitamin D in Suppressing Cytokine Storm in COVID-19 Patients and Associated Mortality

text: The authors have withdrawn this manuscript because they have noticed idiosyncrasies in the reporting of 25(OH)D data across different countries. Therefore, the authors do not wish this work to be cited until after this issue is addressed. If you have any questions, please contact the corresponding author.


title: INFEKTA: A General Agent-based Model for Transmission of Infectious Diseases: Studying the COVID-19 Propagation in Bogotá - Colombia

text: The transmission dynamics of the coronavirus - COVID-19- have challenged humankind at almost every level. Currently, research groups around the globe are trying to figure out such transmission dynamics using different scientific and technological approaches. One of those is by using mathematical and computational models like the compartmental model or the agent-based models. In this paper, a general agent-based model, called INFEKTA, that combines the transmission dynamics of an infectious disease with agents (individuals) that can move on a complex network of accessible places defined over a Euclidean space representing a real town or city is proposed. The applicability of INFEKTA is shown by modeling the transmission dynamics of the COVID-19 in Bogotá city, the capital of Colombia.


title: If the link missed:Could inflammatory skin disorders with barrier dysfunction increase the risk of COVID-19?

text: Since the end of 2019, COVID-19 pandemic caused by the SARS-CoV-2 emerged globally. The angiotensin-converting enzyme 2 (ACE2) on the cell surface is crucial for SARS-COV-2 entering into the cells. The expression of ACE2 in skin suggested that skin might be a way of transmitting SARS-CoV-2. We found the elevated ACE2 level of patients with psoriasis but downregulated after IL-17 antibody treatment. Further results showed that ACE2 expression increased either in psoriasis or in atopic dermatitis, which were typical inflammatory skin disorders with barrier dysfunction. And elevated ACE2 level was also detected in mouse models of dermatitis induced by imiquimod, calcipotriol, repeated tape-stripping or 1-Fluoro-2,4-dinitrobenzene (DNFB) respectively. Moreover, alleviation of cutaneous inflammation with skin recovery moisture also lowered expression of ACE2 in mouse models with barrier deteriorated inflammatory skin disorders. Furthermore, inflammatory skin disorders with barrier dysfunction increased the penetration of topical FITC conjugated spike protein into the skin. Conversely, improvement in skin permeability barrier could prevent this penetration. Thus, indicating the special link between inflammatory skin disorders with skin barrier dysfunction and increasing risk of COVID-19.


title: Lopinavir-ritonavir alone or combined with arbidol in the treatment of 73 hospitalized patients with COVID-19: a pilot retrospective study

text: Objectives: This study aimed to evaluate the antiviral efficacy of lopinavir/ritonavir alone or combined with arbidol in the treatment of hospitalized patients with common coronavirus disease-19 (COVID-19). Methods: In this retrospective observational study, COVID-19 hospitalized patients were identified and divided into two groups based on the antiviral agents used during their hospitalization. Group-LR patients were treated with single antiviral drug of lopinavir-ritonavir. Group-LR+Ar patients were treated with lopinavir-ritonavir combined with arbidol for antiviral therapy at least 3 days. Patients were assessed for different clinical outcomes. Results: A total of 34 and 39 patients were identified for Group-LR and Group-LR+Ar, respectively. Treatment with lopinavir-ritonavir alone was not difference from lopinavir-ritonavir combined with arbidol in overall cure rate of COVID-19 hospitalized patients (92.3% and 97.1%, respectively). In a modified intention-to-treat analysis, lopinavir-ritonavir combined with abidol led to a median time of hospital stay that was shorter by 1.5 days than group-LR (12.5 days vs. 14 days). The percentages of COVID-19 RNA clearance was 92.3 in group-LR and 97.1 in group-LR+Ar. The mean time of virus turning negative was 11.5 plus-or-minus sign 9.0 days in group-LR+Ar that were longer than group-LR. Treatment of lopinavir-ritonavir combined with arbidol did not significantly accelerate main symptoms improvement and promote the image absorption of pulmonary inflammation. Conclusion: No benefit was observed in the anti-virus effect of lopinavir-ritonavir combined with arbidol compared with lopinavir-ritonavir alone in the hospitalized patients with COVID-19. More clinical observations in COVID-19 patients may help to confirm or exclude the effect of antiviral agents.


docid: qkadqohe

title: Tracking the onset date of the community spread of SARS-CoV-2 in Western Countries

text: The SARS-CoV-2 rapidly spread around the world during 2020, but the precise time in which the virus began to spread locally is currently unknown for most countries. Here, we estimate the probable onset date of the community spread of SARS-CoV-2 from the cumulative number of deaths reported during the early stage of the epidemic in Western Europe and the Americas. Our results support that SARS-CoV-2 probably started to spread locally in all western countries analyzed between the middle of January and early February 2020, thus long before community transmission was officially recognized and control measures were implemented.


title: deepMINE - Natural Language Processing based Automatic Literature Mining and Research Summarization for Early-Stage Comprehension in Pandemic Situations specifically for COVID-19

text: The recent pandemic created due to Novel Coronavirus (nCOV-2019) from Wuhan, China demanding a large scale of a general health emergency. This demands novel research on the vaccine to fight against this pandemic situation, re-purposing of the existing drugs, phylogenetic analysis to identify the origin and determine the similarity with other known viruses, etc. The very preliminary task from the research community is to analyze the wide verities of existing related research articles, which is very much time-consuming in such situations where each minute counts for saving hundreds of human lives. The entire manual processing is even lower down the efficiency in mining the information. We have developed a complete automatic literature mining system that delivers efficient and fast mining from existing biomedical literature databases. With the help of modern-day deep learning algorithms, our system also delivers a summarization of important research articles that provides ease and fast comprehension of critical research articles. The system is currently scanning nearly 1,46,115,136 English words from 29,315 research articles in not greater than 1.5 seconds with multiple search keywords. Our research article presents the criticality of literature mining, especially in pandemic situations with the implementation and online deployment of the system.


title: The WD and linker domains of ATG16L1 required for non-canonical autophagy limit lethal respiratory infection by influenza A virus at epithelial surfaces

text: Respiratory viruses such as influenza A virus (IAV) and SARS-CoV-2 (Covid-19) cause pandemic infections where cytokine storm syndrome, lung inflammation and pneumonia lead to high mortality. Given the high social and economic cost of these viruses, there is an urgent need for a comprehensive understanding of how the airways defend against virus infection. Viruses entering cells by endocytosis are killed when delivered to lysosomes for degradation. Lysosome delivery is facilitated by non-canonical autophagy pathways that conjugate LC3 to endo-lysosome compartments to enhance lysosome fusion. Here we use mice lacking the WD and linker domains of ATG16L1 to demonstrate that non-canonical autophagy protects mice from lethal IAV infection of the airways. Mice with systemic loss of non-canonical autophagy are exquisitely sensitive to low-pathogenicity murine-adapted IAV where extensive viral replication throughout the lungs, coupled with cytokine amplification mediated by plasmacytoid dendritic cells, leads to fulminant pneumonia, lung inflammation and high mortality. IAV infection was controlled within epithelial barriers where non-canonical autophagy slowed fusion of IAV with endosomes and reduced activation of interferon signalling. This was consistent with conditional mouse models and ex vivo analysis showing that protection against IAV infection of lung was independent of phagocytes and other leukocytes. This establishes non-canonical autophagy pathways in airway epithelial cells as a novel innate defence mechanism that can restrict IAV infection and lethal inflammation at respiratory surfaces.


title: Stress and coping in the time of COVID-19: Pathways to resilience and recovery

text: Coronavirus Disease 2019 (COVID-19) has disrupted virtually every aspect of daily living, engendering forced isolation and social distance, economic hardship, fears of contracting a potentially lethal illness and feelings of helplessness and hopelessness. Unfortunately, there is no formula or operating manual for how to cope with the current global pandemic. Previous research has documented an array of responses to mass crises or disasters, including chronic anxiety and posttraumatic stress as well as resilience and recovery. Much can be learned from this research about how people have coped in the past in order to identify strategies that may be particularly effective in managing distress and cultivating resilience during these perilous times. We delineate multiple coping strategies (e.g., behavioral activation, acceptance-based coping, mindfulness practice, loving-kindness practices) geared to decrease stress and promote resilience and recovery. These strategies may be especially effective because they help individuals make meaning, build distress tolerance, increase social support, foster a view of our deep human interconnectedness, and take goal-directed value-driven actions in midst of the COVID-19 pandemic.


First Person: Just Doing My Job, not Just for COVID-19 Patients, but for Everyone Every Day


title: A Library of Nucleotide Analogues Terminate RNA Synthesis Catalyzed by Polymerases of Coronaviruses Causing SARS and COVID-19

text: SARS-CoV-2, a member of the coronavirus family, is responsible for the current COVID-19 worldwide pandemic. We previously demonstrated that five nucleotide analogues inhibit the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), including the active triphosphate forms of Sofosbuvir, Alovudine, Zidovudine, Tenofovir alafenamide and Emtricitabine. We report here the evaluation of a library of additional nucleoside triphosphate analogues with a variety of structural and chemical features as inhibitors of the RdRps of SARS-CoV and SARS-CoV-2. These features include modifications on the sugar (2’ or 3’ modifications, carbocyclic, acyclic, or dideoxynucleotides) or on the base. The goal is to identify nucleotide analogues that not only terminate RNA synthesis catalyzed by these coronavirus RdRps, but also have the potential to resist the viruses’ exonuclease activity. We examined these nucleotide analogues with regard to their ability to be incorporated by the RdRps in the polymerase reaction and then prevent further incorporation. While all 11 molecules tested displayed incorporation, 6 exhibited immediate termination of the polymerase reaction (Carbovir triphosphate, Ganciclovir triphosphate, Stavudine triphosphate, Entecavir triphosphate, 3’-O-methyl UTP and Biotin-16-dUTP), 2 showed delayed termination (Cidofovir diphosphate and 2’-O-methyl UTP), and 3 did not terminate the polymerase reaction (2’-fluoro-dUTP, 2’-amino-dUTP and Desthiobiotin-16-UTP). The coronavirus genomes encode an exonuclease that apparently requires a 2’ -OH group to excise mismatched bases at the 3’-terminus. In this study, all of the nucleoside triphosphate analogues we evaluated form Watson-Cricklike base pairs. All the nucleotide analogues which demonstrated termination either lack a 2’-OH, have a blocked 2’-OH, or show delayed termination. These nucleotides may thus have the potential to resist exonuclease activity, a property that we will investigate in the future. Furthermore, prodrugs of five of these nucleotide analogues (Brincidofovir/Cidofovir, Abacavir, Valganciclovir/Ganciclovir, Stavudine and Entecavir) are FDA approved for other viral infections, and their safety profile is well known. Thus, they can be evaluated rapidly as potential therapies for COVID-19.


title: From Isolation to Coordination: How Can Telemedicine Help Combat the COVID-19 Outbreak?

text: The rapid spread of Coronavirus disease 2019 (COVID-19) presents China with a critical challenge. As normal capacity of the Chinese hospitals is exceeded, healthcare professionals struggling to manage this unprecedented crisis face the difficult question of how best to coordinate the medical resources used in highly separated locations. Responding rapidly to this crisis, the National Telemedicine Center of China (NTCC), located in Zhengzhou, Henan Province, has established the Emergency Telemedicine Consultation System (ETCS), a telemedicine-enabled outbreak alert and response network. ETCS is built upon a doctor-to-doctor (D2D) approach, in which health services can be accessed remotely through terminals across hospitals. The system architecture of ETCS comprises three major architectural layers: (1) telemedicine service platform layer, (2) telemedicine cloud layer, and (3) telemedicine service application layer. Our ETCS has demonstrated substantial benefits in terms of the effectiveness of consultations and remote patient monitoring, multidisciplinary care, and prevention education and training.


title: Countries should aim to lower the reproduction number R close to 1.0 for the short-term mitigation of COVID-19 outbreaks

text: The COVID-19 pandemic is still in its early stages and given the speed and magnitude of local outbreaks it is urgent to understand how mitigation measures translate into changes in key epidemiological and clinical outcomes. Here, we employ a mathematical model to explore the short-term consequences of lowering the reproduction number number R0 and delaying measures on total infections and fatalities. The positive implications of mitigation generally accrue as these measures are adopted early, with the most striking effects seen when the reproductive number is lowered to a level Rc≈1.0. As the delay in adopting measures exceeds approximately the half-way point to the peak of an outbreak, the effects of lowering R0 markedly decrease. Aiming for reproduction numbers close to 1.0 can substantially reduce fatality probabilities over short time scales, particularly for larger populations. We conclude that research is urgently needed on how mitigation measures impact R0 and how these can be optimized so as to achieve Rc≈1.0 whilst supporting individual freedoms, society and the economy.


title: Effects of temperature variation and humidity on the mortality of COVID-19 in Wuhan

text: Object Meteorological parameters are the important factors influencing the infectious diseases like severe acute respiratory syndrome (SARS). This study aims to explore the association between coronavirus disease (COVID-19) death and weather parameters. Methods In this study, we collected the daily death number of COVID-19, meteorological and air pollutant data from 20 January, 2020 to 29 February, 2020 in Wuhan, China. Then, the generalized additive model was applied to explore the impact of temperature, humidity and diurnal temperature range on daily mortality of COVID-19. Results There were in total 2299 COVID-19 mortality counts in Wuhan. A positive association with COVID-19 mortality was observed for diurnal temperature range (r = 0.44), but negative association for relative humidity (r = -0.32). In addition, each 1 unit increase in diurnal temperature range was only associated with a 2.92% (95% CI: 0.61%, 5.28%) increase in COVID-19 mortality at lag 3. However, both per 1 unit increase of temperature and absolute humidity were related to the decreased COVID-19 mortality at lag 3 and lag 5, respectively. Conclusion In summary, this study suggests the temperature variation and humidity may be important factors affecting the COVID-19 mortality.


title: Trends in Transmissibility of 2019 Novel Coronavirus-infected Pneumonia in Wuhan and 29 Provinces in China

text: Background: The 2019 novel coronavirus infected pneumonia (COVID- 19) represents a significant public health threat. The COVID-19 emerged in December 2019 in Wuhan, China and rapidly spread to other regions and countries. The variation in transmission patterns and disease spread in regard to time or among different locations, partially reflecting the public health in- tervention effects, remains to be quantified. As most transmissibility-related epidemic parameters are unknown, we sought, with minimal assumptions, to estimate real-time transmissibility and forecast new cases using dynamic modelling. Method: Using the cases reported from the National Health Commission of China and transportation data, including the total number of travelling hours through railway, airplane, and car outbound from Wuhan, we have built a time-series model to estimate real-time underlying transmission rates of newly generated cases sequentially from January 20, 2020 to Feb 13, 2020 in Wuhan, Hubei province and other 28 provinces in China. We quantified the instantaneous transmission rate and relative reproduction number (R_t) of COVID-19, and evaluated whether public health intervention affected the case transmissibility in each province. Based on the current estimates, we have predicted the trend of disease spread with a high level of certainty. Findings: We estimated that R_t declined from the range of 4 to 5 towards 1 and remained below unity, while there was an initial growth followed by a decline in a shorter period in Hubei and other provinces. The ratio of transmission rates decreased dramatically from January 23 to 27 likely due to the rigorous public health intervention implemented by the government beginning on January 23, 2020. The mean duration of the infectious period was 6 to 9 days. We have predicted the trend of infection sizes which be- came stable in provinces around February 19 to 24, 2020, and the date of containment would be one-week later in Wuhan. Interpretation: Public health interventions implemented at both the so- cial and personal levels are effective in preventing outbreaks of COVID-19 in Wuhan and other provinces. Model prediction results suggested that COVID- 19 will be contained around the end of February 2020 in China. Keywords: Coronavirus, COVID-19, transmissibility, dynamic reproduction number R, statistical modelling, pneumonia outbreak


title: Geographies of Covid-19: how space and virus shape each other

text: This paper contributes to a geographically-informed preliminary assessment of the diverse and uneven immediate impacts of the Covid-19 pandemic, and outlines an agenda for geographical studies of its longer term effects. Intrigued by the apparent tendency of an inverse relationship between a country’s health security capacities and Covid-19 mortalities, the paper explores the significance of a range of geographically situated contextual factors in the realms of the economy, governance and culture as mediators of the public health impacts of Covid-19, and questions how these realms may also be reshaped by this viral pandemic. The paper concludes with reflections on the path dependency and state centrality of pandemic response, and the potential post-pandemic reconfiguration of state-market-society relationships.


title: Mass spectrometry analysis of newly emerging coronavirus HCoV-19 spike S protein and human ACE2 reveals camouflaging glycans and unique post-translational modifications

text: The pneumonia-causing COVID-19 pandemia has prompt worldwide efforts to understand its biological and clinical traits of newly identified HCoV-19 virus. In this study, post-translational modification (PTM) of recombinant HCoV-19 S and hACE2 were characterized by LC-MSMS. We revealed that both proteins were highly decorated with specific proportions of N-glycan subtypes. Out of 21 possible glycosites in HCoV-19 S protein, 20 were confirmed completely occupied by N-glycans, with oligomannose glycans being the most abundant type. All 7 possible glycosylation sites in hACE2 were completely occupied mainly by complex type N-glycans. However, we showed that glycosylation did not directly contribute to the binding affinity between SARS-CoV spike protein and hACE2. Additionally, we also identified multiple sites methylated in both proteins, and multiple prolines in hACE2 were converted to hydroxylproline. Refined structural models were built by adding N-glycan and PTMs to recently published cryo-EM structure of the HCoV-19 S and hACE2 generated with glycosylation sites in the vicinity of binding surface. The PTM and glycan maps of both HCoV-19 S and hACE2 provide additional structural details to study mechanisms underlying host attachment, immune response mediated by S protein and hACE2, as well as knowledge to develop remedies and vaccines desperately needed nowadays.


Addressing therapeutic questions to help Canadian health care professionals optimize COPD management for their patients during the COVID-19 pandemic


title: GW190814: Gravitational Waves from the Coalescence of a 23 M$_\odot$ Black Hole with a 2.6 M$_\odot$ Compact Object

text: We report the observation of a compact binary coalescence involving a 22.2 - 24.3 $M_{\odot}$ black hole and a compact object with a mass of 2.50 - 2.67 $M_{\odot}$ (all measurements quoted at the 90$\%$ credible level). The gravitational-wave signal, GW190814, was observed during LIGO's and Virgo's third observing run on August 14, 2019 at 21:10:39 UTC and has a signal-to-noise ratio of 25 in the three-detector network. The source was localized to 18.5 deg$^2$ at a distance of $241^{+41}_{-45}$ Mpc; no electromagnetic counterpart has been confirmed to date. The source has the most unequal mass ratio yet measured with gravitational waves, $0.112^{+0.008}_{-0.009}$, and its secondary component is either the lightest black hole or the heaviest neutron star ever discovered in a double compact-object system. The dimensionless spin of the primary black hole is tightly constrained to $\leq 0.07$. Tests of general relativity reveal no measurable deviations from the theory, and its prediction of higher-multipole emission is confirmed at high confidence. We estimate a merger rate density of 1-23 Gpc$^{-3}$ yr$^{-1}$ for the new class of binary coalescence sources that GW190814 represents. Astrophysical models predict that binaries with mass ratios similar to this event can form through several channels, but are unlikely to have formed in globular clusters. However, the combination of mass ratio, component masses, and the inferred merger rate for this event challenges all current models for the formation and mass distribution of compact-object binaries.


title: Effectiveness and cost-effectiveness of public health measures to control COVID-19: a modelling study

text: Background The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was first reported in China, which caused a respiratory disease known as Coronavirus Disease 2019 (COVID-19). Since its discovery, the virus has spread to over 100 countries and claimed more than 4000 deaths. This study aimed to assess the effectiveness and cost-effectiveness of various response public health measures. Method The stochastic agent-based model was used to simulate the process of COVID-19 outbreak in scenario I (imported one case) and II (imported four cases) with a series of public health measures, involving the personal protection, isolation-and-quarantine, gathering restriction, and community containment. The virtual community was constructed following the susceptible-latent-infectious-recovered framework. The epidemiological and economic parameters derived from the previous literature and field investigation. The main outcomes included avoided infectors, cost-effectiveness ratios (CERs), and incremental cost-effectiveness ratios (ICERs). The sensitivity analyses were undertaken to assess uncertainty. Findings In scenario I and II, the isolation-and-quarantine averted 1696 and 1990 humans infected respectively at the cost of US$12 428 and US$58 555, both with negative value of ICERs. The joint strategy of personal protection and isolation-and-quarantine could avert one more case than single isolation-and-quarantine with additional cost of US$ 166 871 and US$180 140 respectively. The effectiveness of isolation-and-quarantine decreased as lowering quarantine probability and increasing delay-time. Especially in scenario II, when the quarantine probability was less than 25%, the number of infections raised sharply; when the quarantine delay-time reached six days, more than a quarter of individuals would be infected in the community. The strategy including community containment could protect more lives and was cost-effective, when the number of imported cases was no less than 65, or the delay-time of quarantine was more than five days, or the quarantine probability was below 25%, based on current assumptions. Interpretation The isolation-and-quarantine was the most cost-effective intervention. However, personal protection and isolation-and-quarantine was the optimal strategy averting more infectors than single isolation-and-quarantine. Certain restrictions should be considered, such as more initial imported cases, longer quarantine delay-time and lower quarantine probability.


title: Patient-Led COVID-19 Triage Systems and Case Fatality Rates: A Comparative Study Between Singapore, Japan, Norway, the USA and the UK.

text: Introduction: The case fatality rate from COVID-19 differs markedly around the world. There are likely a number of factors one can attribute to such disparity, not least of which is differing healthcare models and approaches. Here, we examine the COVID-19 related health advice issued by six different countries, specifically examining the patient-led triage pathways in each country. Methods: A simulation study was conducted on current, nationwide, patient-led triage systems from three countries with low case fatality rates (Singapore, Norway and Japan) and two countries with high case fatality rates (the USA and the UK). 36 case scenarios were designed to imitate common presentations of COVID-19 with varying degrees of severity. These scenarios were then fed into each countrys patient-led triage system. The advice for each scenario was recorded and then compared. Results: Patient-led triage systems from Singapore, Japan and Norway maintained a low threshold for advising clinical contact for patients with possible COVID-19 (88 to 100% of cases were referred). Patient-led triage systems from the USA and the UK maintained high thresholds for advising contact with either call centre support or clinical contact (28 and 33% of cases were referred, respectively), and triaged the majority of cases home with no further healthcare input. There was a strong inverse correlation between percentage of cases referred and the nations case fatality rate (Pearsons Correlation = -0.642, p = 0.01). Conclusion: In this simulation study, countries with low case fatality rates - Singapore, Norway and Japan -, performed well, successfully identifying severe COVID-19 and triaging such cases to medical care. The USA triage system (CDCs Coronavirus Self-Checker) and the UKs triage system (NHS 111 online) performed poorly, failing to identify Severe COVID-19 infection and sepsis in the case simulations, and triaging the majority of cases to self-care with no further healthcare input. Such poorly performing triage systems are likely to be contributing to the high case fatality rates in the US and the UK.


title: FSC-Q: A CryoEM map-to-atomic model quality validation based on the local Fourier Shell Correlation

text: In recent years, advances in cryoEM have dramatically increased the resolution of Coulomb potential maps and, with it, the number of solved atomic models. It is widely accepted that the quality of cryoEM maps varies locally; therefore, the evaluation of the maps-derived structural models must be done locally as well. In this article, a method for the local analysis of the map-to-model fit is presented. The algorithm uses a comparison of two local resolution maps. The first is the local FSC (Fourier shell correlation) between the full map and the model, while the second is calculated between the half maps normally used in typical single particle analysis workflows. We call the new quality measure “FSC-Q”, and it is a quantitative estimation of how much of the model is supported by the signal content of the map. Furthermore, we show that FSC-Q may be helpful to avoid overfitting. It can be used to complement other methods, such as the Q-score method that estimates the resolvability of atoms.


title: Increasing Virus Test Capacity via Recursive Pool Testing with an Application to SARS-CoV-2 Testing

text: In the context of adequate reactions to the current Covid-19 pandemic, Seifried, Ciesek et al. [6, 5] have proposed the application of SARS-CoV-2 pool testing in the pursuit of increasing testing capacity. We show how this method can be substantially improved in realistic scenarios, and we point out a possible impact on the ongoing discussion concerning the need of increased testing as a complementary measure to relaxed restrictions.


title: New corona virus (COVID-19) management in pregnancy and childbirth

text: Context: Coronavirus disease 2019 (COVID-19) is an emerging disease that has been associated with a rapid increase in afflicted cases and deaths since its first introduction in Wuhan, China, in December 2019. The emerging infection can have a significant impact on pregnant women and the fetus. The purpose of this study was to review and summarize the latest research on the management and treatment of women in pregnancy and childbirth in the world and management protocols available in Iran and other countries. Evidence Acquisition: In this review study, we examined Persian and English studies by searching the Pubmed, Web of Science, UpToDate, SID, Scopus, Google Scholar, and medRxiv databases with keywords pregnant, pregnancy, gravidity, coronavirus, infec-tion, COVID-19, and their Persian equivalents. Articles and reviews were on humans. After reviewing and removing duplicate and non-eligible articles, 12 articles and 11 guidelines and recommendations were obtained. Results: The results of the review study were categorized as follows: clinical course of COVID-19 in pregnancy, perinatal outcomes, neonatal outcomes, vertical transmission potential, management of COVID-19 in pregnancy, labor, and delivery in women, postpartum stage in women with COVID-19, breastfeeding, and care for a infant born to a mother with COVID-19. The general princi-ples of caring for women in pregnancy and childbirth included early separation, using aggressive infection control methods, non-administration of corticosteroids repeatedly, oxygen therapy, preventing from fluid overload, using empirical antibiotics (due to the risk of secondary bacterial infection), co-infection testing of other infections, avoiding breastfeeding in mothers with definitive positive tests, and being cautious in suspicious cases. Conclusions: Given the limited information on the complications and outcomes of the virus in pregnancy and childbirth and the increasing number of studies, the provision of up-to-date care according to global and regional processes and guidelines is recommended for mothers affected and suspected with COVID-19.


title: iSCAN: An RT-LAMP-coupled CRISPR-Cas12 module for rapid, sensitive detection of SARS-CoV-2

text: The COVID-19 pandemic caused by SARS-CoV-2 affects all aspects of human life. Detection platforms that are efficient, rapid, accurate, specific, sensitive, and user friendly are urgently needed to manage and control the spread of SARS-CoV-2. RT-qPCR based methods are the gold standard for SARS-CoV-2 detection. However, these methods require trained personnel, sophisticated infrastructure, and a long turnaround time, thereby limiting their usefulness. Reverse transcription-loop-mediated isothermal amplification (RT-LAMP), a one-step nucleic acid amplification method conducted at a single temperature, has been used for colorimetric virus detection. CRISPR-Cas12 and CRISPR-Cas13 systems, which possess collateral activity against ssDNA and RNA, respectively, have also been harnessed for virus detection. Here, we built an efficient, rapid, specific, sensitive, user-friendly SARS-CoV-2 detection module that combines the robust virus amplification of RT-LAMP with the specific detection ability of SARS-CoV-2 by CRISPR-Cas12. Furthermore, we combined the RT-LAMP-CRISPR-Cas12 module with lateral flow cells to enable highly efficient point-of-care SARS-CoV-2 detection. Our iSCAN SARS-CoV-2 detection module, which exhibits the critical features of a robust molecular diagnostic device, should facilitate the effective management and control of COVID-19.