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

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


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

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


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

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


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

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


docid: mmcszoxb

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

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


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

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


title: Ranking the effectiveness of worldwide COVID-19 government interventions

text: Non-pharmaceutical interventions (NPIs) to mitigate the spread of SARS-CoV-2 were often implemented under considerable uncertainty and a lack of scientific evidence. Assessing the effectiveness of the individual interventions is critical to inform future preparedness response plans. Here we quantify the impact of 4,579 NPIs implemented in 76 territories on the effective reproduction number, Rt, of COVID-19. We use a hierarchically coded data set of NPIs and propose a novel modelling approach that combines four computational techniques, which together allow for a worldwide consensus rank of the NPIs based on their effectiveness in mitigating the spread of COVID-19. We show how the effectiveness of individual NPIs strongly varies across countries and world regions, and in relation to human and economic development as well as different dimensions of governance. We quantify the effectiveness of each NPI with respect to the epidemic age of its adoption, i.e., how early into the epidemics. The emerging picture is one in which no one-fits-all solution exists, and no single NPI alone can decrease Rt below one and that a combination of NPIs is necessary to curb the spread of the virus. We show that there are NPIs considerably less intrusive and costly than lockdowns that are also highly effective, such as certain risk communication strategies and voluntary measures that strengthen the healthcare system. By allowing to simulate ``what-if'' scenarios at the country level, our approach opens the way for planning the most likely effectiveness of future NPIs.


title: Projecting the transmission dynamics of SARS-CoV-2 through the post-pandemic period

text: There is an urgent need to project how transmission of the novel betacoronavirus SARS-CoV-2 will unfold in coming years. These dynamics will depend on seasonality, the duration of immunity, and the strength of cross-immunity to/from the other human coronaviruses. Using data from the United States, we measured how these factors affect transmission of human betacoronaviruses HCoV-OC43 and HCoV-HKU1. We then built a mathematical model to simulate transmission of SARS-CoV-2 through the year 2025. We project that recurrent wintertime outbreaks of SARS-CoV-2 will probably occur after an initial pandemic wave. We summarize the full range of plausible transmission scenarios and identify key data still needed to distinguish between them, most importantly longitudinal serological studies to determine the duration of immunity to SARS-CoV-2.


title: Targeted Oxidation Strategy (TOS) for Potential Inhibition of Coronaviruses by Disulfiram — a 70-Year Old Anti-Alcoholism Drug

text: In the new millennium, the outbreak of new coronavirus has happened three times: SARS-CoV, MERS-CoV, and 2019-nCoV Unfortunately, we still have no pharmaceutical weapons against the diseases caused by these viruses The pandemic of 2019-nCoV reminds us of the urgency to search new drugs with totally different mechanism that may target the weaknesses specific to coronaviruses Herein, we disclose a new targeted oxidation strategy (TOS II) leveraging non-covalent interactions potentially to oxidize and inhibit the activities of cytosolic thiol proteins via thiol/thiolate oxidation to disulfide (TOD) Quantum mechanical calculations show encouraging results supporting the feasibility to selectively oxidize thiol of targeted proteins via TOS II even in relatively reducing cytosolic microenvironments Molecular docking against the two thiol proteases Mpro and PLpro of 2019-nCoV provide evidence to support a TOS II mechanism for two experimentally identified anti-2019-nCoV disulfide oxidants: disulfiram and PX-12 Remarkably, disulfiram is an anti-alcoholism drug approved by FDA 70 years ago, thus it can be immediately used in phase III clinical trial for anti-2019-nCoV treatment Finally, a preliminary list of promising TOS II drug candidates targeting the two thiol proteases of 2019-nCoV are proposed upon virtual screening of 32143 disulfides


title: Explaining national differences in the mortality of Covid-19: individual patient simulation model to investigate the effects of testing policy and other factors on apparent mortality.

text: There has been extensive speculation on the apparent differences in mortality between countries reporting on the confirmed cases and deaths due to Covid-19. A number of explanations have been suggested, but there is no clear evidence about how apparent fatality rates may be expected to vary with the different testing regimes, admission policies and other variables. An individual patient simulation model was developed to address this question. Parameters and sensitivity analysis based upon recent international data sources for Covid-19 and results were averaged over 100 iterations for a simulated cohort of over 500,000 patients. Different testing regimes for Covid-19 were considered; testing admitted patients only, various rates of community testing of symptomatic cases and active contact-tracing and screening. In the base case analysis, apparent mortality ranged from 10.5% under a policy of testing only admitted patients to 0.4% with intensive contact tracing and community testing. These findings were sensitive to assumptions regarding admission rates and the rate of spread, with more selective admission policies and suppression of spread increasing the apparent mortality and the potential for apparent mortality rates to exceed 18% under some circumstances. Under all scenarios the proportion of patients tested in the community had the greatest impact on apparent mortality. Whilst differences in mortality due to health service and demographic factors cannot be excluded, the current international differences in reported mortality are all consistent with differences in practice regarding screening, community testing and admission policies.


title: The Dynamic Changes of Antibodies against SARS-CoV-2 during the Infection and Recovery of COVID-19

text: Deciphering the dynamic changes of antibodies against SARS-CoV-2 is essential for understanding the immune response in COVID-19 patients. By comprehensively analyzing the laboratory findings of 1,850 patients, we describe the dynamic changes of the total antibody, spike protein (S)-, receptor-binding domain (RBD)-, and nucleoprotein (N)- specific IgM and IgG levels during SARS-CoV-2 infection and recovery. Our results indicate that the S-, RBD-, and N- specific IgG generation of severe/critical COVID-19 patients is one week later than mild/moderate cases, while the levels of these antibodies are 1.5-fold higher in severe/critical patients during hospitalization (P<0.01). The decrease of these IgG levels indicates the poor outcome of severe/critical patients. The RBD- and S-specific IgG levels are 2-fold higher in virus-free patients (P<0.05). Notably, we found that the patients who got re-infected had a low level of protective antibody on discharge. Therefore, our evidence proves that the dynamic changes of antibodies could provide an important reference for diagnosis, monitoring, and treatment, and shed new light on the precise management of COVID-19.


title: HLA genetics and COVID-19

text: Human leukocyte antigens (HLAs) are proteins encoded by a diverse set of human genes in the major histocompatibility complex Most people carry between three and six different HLA alleles that show geographically specific distributions These proteins are important for how the immune system recognizes and mounts immune defenses against infection Nguyen et al examined how HLA variation affects the cellular immune response to peptides from human-infecting coronaviruses The authors found that HLA-B*46:01 had the fewest predicted binding sites to the severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) virus, and HLA-B*15:03 showed the greatest capacity to present highly conserved shared SARS-CoV-2 peptides to immune cells HLA typing may therefore offer valuable information on how coronavirus disease 2019 (COVID-19) might manifest in an individual and help to prioritize treatment options


title: Multi-state epidemic processes on complex networks

text: Infectious diseases are practically represented by models with multiple states and complex transition rules corresponding to, for example, birth, death, infection, recovery, disease progression, and quarantine. In addition, networks underlying infection events are often much more complex than described by meanfield equations or regular lattices. In models with simple transition rules such as the SIS and SIR models, heterogeneous contact rates are known to decrease epidemic thresholds. We analyze steady states of various multi-state disease propagation models with heterogeneous contact rates. In many models, heterogeneity simply decreases epidemic thresholds. However, in models with competing pathogens and mutation, coexistence of different pathogens for small infection rates requires network-independent conditions in addition to heterogeneity in contact rates. Furthermore, models without spontaneous neighbor-independent state transitions, such as cyclically competing species, do not show heterogeneity effects.


docid: kuqinczz

title: Optimizing RT-PCR detection of SARS-CoV-2 for developing countries using pool testing

text: The global shortage of reagents and kits for nucleic acid extraction and molecular detection of SARS-CoV-2, requires new cost-effective strategies for the diagnosis of suspected COVID-19 cases, especially in countries that need to increase detection capacity. Pooled nucleic acid testing has been extensively used as a cost-effective strategy for HIV, HepB, HepC and influenza. Also, protocols dispensing of RNA extraction appears as an attractive option for detection of SARS-CoV-2. In this study, pooling nasopharyngeal samples with both automated and manual extraction proved reliable, and thus a potential efficient alternative for the diagnosis of suspected COVID-19 in developing countries.


title: Michael B.A. Oldstone Ljubisa Vitkovic

text: Unknown


title: Disentangling the Hypothesis of Host Dysosmia and SARS-CoV-2: The Bait Symptom That Hides Neglected Neurophysiological Routes

text: The respiratory condition COVID-19 arises in a human host upon the infection with SARS-CoV-2, a coronavirus that was first acknowledged in Wuhan, China, at the end of December 2019 after its outbreak of viral pneumonia. The full-blown COVID-19 can lead, in susceptible individuals, to premature death because of the massive viral proliferation, hypoxia, misdirected host immunoresponse, microthrombosis, and drug toxicities. Alike other coronaviruses, SARS-CoV-2 has a neuroinvasive potential, which may be associated with early neurological symptoms. In the past, the nervous tissue of patients infected with other coronaviruses was shown to be heavily infiltrated. Patients with SARS-CoV-2 commonly report dysosmia, which has been related to the viral access in the olfactory bulb. However, this early symptom may reflect the nasal proliferation that should not be confused with the viral access in the central nervous system of the host, which can instead be allowed by means of other routes for spreading in most of the neuroanatomical districts. Axonal, trans-synaptic, perineural, blood, lymphatic, or Trojan routes can gain the virus multiples accesses from peripheral neuronal networks, thus ultimately invading the brain and brainstem. The death upon respiratory failure may be also associated with the local inflammation- and thrombi-derived damages to the respiratory reflexes in both the lung neuronal network and brainstem center. Beyond the infection-associated neurological symptoms, long-term neuropsychiatric consequences that could occur months after the host recovery are not to be excluded. While our article does not attempt to fully comprehend all accesses for host neuroinvasion, we aim at stimulating researchers and clinicians to fully consider the neuroinvasive potential of SARS-CoV-2, which is likely to affect the peripheral nervous system targets first, such as the enteric and pulmonary nervous networks. This acknowledgment may shed some light on the disease understanding further guiding public health preventive efforts and medical therapies to fight the pandemic that directly or indirectly affects healthy isolated individuals, quarantined subjects, sick hospitalized, and healthcare workers.


title: Exploring Conformational Transition of 2019 Novel Coronavirus Spike Glycoprotein Between Its Closed and Open States Using Molecular Dynamics Simulations

text: Since its first recorded appearance in December 2019, a novel coronavirus (SARS-CoV-2) causing the disease COVID-19 has resulted in more than 2,000,000 infections and 128,000 deaths. Currently there is no proven treatment for COVID-19 and there is an urgent need for the development of vaccines and therapeutics. Coronavirus spike glycoproteins play a critical role in coronavirus entry into the host cells, as they provide host cell recognition and membrane fusion between virus and host cell. Thus, they emerged as popular and promising drug targets. Crystal structures of spike protein in its closed and open states were resolved very recently in March 2020. These structures comprise 77% of the sequence and provide almost the complete protein structure. Based on down and up positions of receptor binding domain (RBD), spike protein can be in a receptor inaccessible closed or receptor accessible open state, respectively. Starting from closed and open state crystal structures, and also 16 intermediate conformations, an extensive set of all-atom molecular dynamics (MD) simulations in the presence of explicit water and ions were performed. Simulations show that in its down position, RBD has significantly lower mobility compared to its up position; probably caused by the 6 interdomain salt bridges of RBD in down position compared to 3 in up position. Free energy landscapes based on MD simulations revealed a semi-open state located between closed and open states. Minimum energy pathway between down and up positions comprised a gradual salt bridge switching mechanism. Furthermore, although significantly lower than open state, ACE2 binding surface of RBD contained a partial solvent accessibility in its closed state.


docid: nghjkrow

title: Top stories: Bungled coronavirus testing, disarming ‘atomic bomb’ cells, and jet stream blocking

text: Speed is critical in the response to COVID-19 So why has the United States been so slow in its attempt to develop reliable diagnostic tests and use them widely? One answer is that a test kit designed by the U S Centers for Disease Control and Prevention (CDC) and rolled out to state and local labs late last month contained a faulty reagent The problems have led many to doubt the accuracy of confirmed tallies of the disease But the situation may soon improve, as the Food and Drug Administration comes up with a workaround for the faulty CDC kit


title: Countdown to a vaccine

text: More than 100 coronavirus vaccines are in development, but will any of them work?


title: Spatial and temporal dynamics of SARS-CoV-2 in COVID-19 patients: A systematic review

text: Background The spatial and temporal dynamics of SARS-CoV-2 have been mainly described in form of case series or retrospective studies. In this study, we aimed to provide a coherent overview from published studies of the duration of viral detection and viral load in COVID-19 patients, stratified by specimen type, clinical severity and age. Method We systematically searched PubMed/MEDLINE and Cochrane review database for studies published between 1. November 2019 and 23rd of April 2020. We included studies that reported individual viral data over time measuring negative conversion by two consecutive negative tests, individual clinical severity and age. We excluded studies that reported viral data as patient fraction, reported only baseline data, included solely asymptomatic patients or were interventional studies. Extracted data included author, title, design, sample size, thresholds and genes of RT-PCR, patient age, COVID-19 severity, clinical characteristics, treatment, location of viral sampling, duration of viral detection, and viral load. We pooled the data of selected studies to determine effect estimates of duration of viral detection. Combined viral load was visualized over time. Findings Out of 7226 titles screened, 37 studies met the inclusion criteria and were included in the qualitative analysis and 22 studies in the quantitative analysis comprising 650 COVID-19 patients. The pooled estimate of the duration of positive detection of the virus was in mild adult patients 12.1 days (CI: 10.12, 14.05) after symptom onset in the upper respiratory tract (URT), 24.1 days (CI: 10.02, 38.19) in lower respiratory tract (LRT), and 15.5 days (CI: 8.04, 22.88) in faeces. Further, in mild adult patients, the maximum viral load was ~ 6.61 x 108 viral copies/mL in the URT and ~ 2.69 x 108 viral copies/mL in the LRT, within the first week of symptom onset. The maximum viral load in faeces was reported as ~ 3.55 x 107 copies/mL on Day 9. In moderate-severe adult patients, the pooled estimate of mean duration of positive viral detection in the URT was 15.8 days (CI: 11.12, 20.56) after symptom onset, 23.2 days (CI: 21.49, 24.97) in the LRT, 20.8 days (CI: 16.40, 25.17) in faeces. The maximum viral load was 4.60 x 109 copies/mL on Day 8 in the URT, 3.45 x 108 copies/mL on Day 11 in the LRT, 2.76 x 106 copies/mL on Day 18 in faeces and 1 x 104 copies/mL on Day 3 in blood. In children with mild symptoms, the pooled estimate of the mean duration of positive SARS-CoV-2 viral detection was 11.1 days (CI: 7.14, 15.11) in the URT and 16.0 days (CI: 11.49, 20,47) in the faeces, without reporting quantitative viral data. Viral positivity was detected in the urine and eye in one patient. Interpretation Our analysis showed consistent viral detection from specimen from the URT, the LRT and faeces, irrespective of the clinical severity of COVID-19. Our analysis suggests that SARS-CoV-2 persists for a longer duration in the LRT compared to the URT, whereas the differences in the duration of viral detection between mild and moderate-severe patients is limited in the LRT, but an indication of longer duration of viral detection in feces and the URT for moderate-severe patients was shown. Further, viral load was demonstrated to peak in the URT within first weak of infection, whereas maximum viral load has been observed to occur later and within the second week of infection in the LRT. Funding This study was funded by Innovation Fund Denmark.


title: Simulation-based Estimation of the Spread of COVID-19 in Iran

text: Background: The 2019 Coronavirus (COVID-19) has turned into a global pandemic with unprecedented challenges for the global community. Understanding the state of the disease and planning for future trajectories relies heavily on data on the spread and mortality. Yet official data coming from various countries are highly unreliable: symptoms similar to common cold in majority of cases and limited screening resources and delayed testing procedures may contribute to under-estimation of the burden of disease. Anecdotal and more limited data are available, but few have systematically combined those with official statistics into a coherent view of the epidemic. This study is a modeling-in-real-time of the emerging outbreak for understanding the state of the disease. Our focus is on the case of the spread of disease in Iran, as one of the epicenters of the disease in the first months of 2020. Method: We develop a simple dynamic model of the epidemic to provide a more reliable picture of the state of the disease based on existing data. Building on the generic SEIR (Susceptible, Exposed, Infected, and Recovered) framework we incorporate two behavioral and logistical considerations. First we capture the endogenous changes in contact rate (average contact per person) as more death are reported. As a result the reproduction number changes endogenously in the model. Second we differentiate reported and true cases by including simple formulations for how only a fraction of cases might be diagnosed, and how that fraction changes in response to epidemic's progression. In estimating the model we use both the official data as well as the discovered infected travelers and unofficial medical community estimates and triangulate these sources to build a more complete picture. Calibration is completed by forming a likelihood function for observing the actual time series data conditional on model parameters, and conducting a Markov Chain Monte Carlo simulations. The model is used to estimate current "true" cases of infection and death. We analyze the future trajectory of the disease under six conditions related to the seasonal effects and policy measures targeting social distancing. Findings: The model closely replicates the past data but also shows the true number of cases is likely far larger. We estimate about 493,000 current infected cases (90% CI: 271K-810K) as of March 20th, 2020. Our estimate for cumulative cases of infection until that date is 916,000 (90% CI: 508K, 1.5M), and for total death is 15,485 (90% CI: 8.4K, 25.8K). These numbers are significantly (more than one order of magnitude) higher than official statistics. The trajectory of the epidemic until the end of June could take various paths depending on the impact of seasonality and policies targeting social distancing. In the most optimistic scenario for seasonal effects, depending on policy measures, 1.6 million Iranians (90% CI: 0.9M-2.6M) are likely to get infected, and death toll will reach about 58,000 cases (90% CI: 32K-97K), while in the more pessimistic scenarios, death toll may exceed 103,000 cases (90% CI: 56K-172K). Implication: Our results suggest that the number of cases and deaths may be over an order of magnitude larger than official statistics in Iran. Absent extended testing capacity other countries may face a significant under-count of existing cases and thus be caught off guard about the actual toll of the epidemic.


title: A phenomenological algorithm for short-range predictions of the Covid-19 pandemics 2020

text: We present an algorithm for dynamical fitting of a logistic curve to the Covid-19 epidemics data, with fit-parameters linearly evolving to the future. We show that the algorithm would have given reasonable short- and medium-range predictions for the epidemics for several countries.


title: Epidemiological parameter review and comparative dynamics of influenza, respiratory syncytial virus, rhinovirus, human coronavirus, and adenovirus

text: Influenza-like illness (ILI) accounts for a large burden of annual morbidity and mortality worldwide. A finer-grained knowledge of the parameters and dynamics of the viruses commonly underlying ILI is needed for modeling, diagnostic, and intervention efforts. We conducted an extensive literature review for epidemiological parameter values for influenza, respiratory syncytial virus (RSV), rhinovirus, human coronavirus (HCoV), and adenovirus. We also developed a deterministic SEIR model for ILI, and derived an expression for R0. We here report ranges and means for parameters for these five common viruses.


SARS-CoV-2 exposure, symptoms and seroprevalence in health care workers


title: Tube thoracostomy during the COVID-19 pandemic: guidance and recommendations from the AAST Acute Care Surgery and Critical Care Committees

text: This document provides guidance for trauma and acute care surgeons surrounding the placement, management and removal of chest tubes during the COVID-19 pandemic.


title: Dynamic models for Coronavirus Disease 2019 and data analysis

text: In this letter, two time delay dynamic models, a Time Delay Dynamical–Novel Coronavirus Pneumonia (TDD‐NCP) model and Fudan‐Chinese Center for Disease Control and Prevention (CCDC) model, are introduced to track the data of Coronavirus Disease 2019 (COVID‐19). The TDD‐NCP model was developed recently by Chengąŕs group in Fudan and Shanghai University of Finance and Economics (SUFE). The TDD‐NCP model introduced the time delay process into the differential equations to describe the latent period of the epidemic. The Fudan‐CDCC model was established when Wenbin Chen suggested to determine the kernel functions in the TDD‐NCP model by the public data from CDCC. By the public data of the cumulative confirmed cases in different regions in China and different countries, these models can clearly illustrate that the containment of the epidemic highly depends on early and effective isolations.


The role of angiotensin-converting-enzyme 2 in the age-and sex related poor prognosis of COVID-19. A comment on recent findings on novel coronavirus infection by sars-coV-2


COVID-19 impact on urology practice_ A possible dilemma of misdiagnosis


title: Drive-through testing for SARS-CoV-2 in symptomatic health and social care workers and household members: an observational cohort study in Tayside, Scotland

text: It has been recognised that health and social care workers (HSCW) experience higher rates of infection with SARS-CoV-2. Widespread testing of HSCWs and their symptomatic household contacts (SHCs) has not been fully implemented in the United Kingdom. We describe the results of a testing programme for HSCWs and SHCs in a single UK region (Tayside, Scotland). The testing service was established 17 th March 2020 as the first in the country, and samples were collected at a drive-through testing hub based at a local community hospital. HSCWs with mild symptoms who were self-isolating and the SHCs of HSCWs who would therefore be absent from work attended for testing. From 17 th March 2020 to 11 th April, 1887 HSCWs and SHCs underwent testing. Clinical information was available for 1727 HSCWs and SHCs. 4/155 (2.6%) child contacts, 73/374 (19.5%) adult contacts and 325/1173 (27.7%) HSCWs tested positive for SARS-CoV-2. 15 of 188 undetermined cases were positive (8.0%). We estimate that testing prevented up to 3634 lost work days from HSCW testing, 2795 from adult SHC testing and 1402 lost work days from child SHC testing. The establishment of this testing programme has assisted the infection prevention and control team in their investigation of transmission and supported adequate staffing in health and social care sectors.


title: Clinical features and outcomes of 2019 novel coronavirus-infected patients with cardiac injury

text: Aims To explore the epidemiological and clinical features of 2019 novel coronavirus(2019-nCoV)-infected patients with cardiac injury . Methods and results Data were collected from patients medical records, and we defined cardiac injury according to cardiac biomarker troponin I level > 0.03>ug/L. Among the 291 patients, 15 (5.2%) showed evidence of cardiac injury. Of 16 hospitalized patients with cardiac injury, the median age was 62 years, and 11/15 (73.3%) were men. Underlying cardiovascular diseases in some patients were hypertension (n=7, 46.6%), coronary heart disease (n=3, 20%) and diabetes (n=3, 20%). The most common symptoms at illness onset in patients with cardiac injury were fever (n=11, 73.3%), cough (n=7, 46.7%), headache or fatigue (n=5, 33.3%) and dyspnoea (n=4, 26.6%). These patients had higher systolic pressures, and lower lymphocyte counts and platelet counts, compared with patients without cardiac injury, respectively. Bilateral infiltrates on chest X-ray and elevated C-reactive protein occurred in all patients with cardiac injury. Compared with patients without cardiac injury, patients with cardiac injury were more likely to develop acute respiratory distress syndrome (73.3%), and receive mechanical ventilation (53.4%), continuous renal replacement therapy (33.3%), extracorporeal membrane oxygenation (26.7%) and vasopressor therapy (26.7%) and be admitted to the intensive care unit (73.3%). One patient died during the study. Conclusion Cardiac injury is a common condition among patients infected with 2019-nCoV.Compared with patients without cardiac injury, the clinical outcomes of patients with cardiac injury are relatively worse. Keywords: 2019-nCoV, Cardiac injury, Clinical features


title: ‘Keeping the kids at home’ can limit the persistence of contagious pathogens in social animals

text: In social species where offspring are reared together in communal burrows or similar structures, young animals typically do not engage in between-group contact during their development – a behavioural trait we call ‘offspring with restricted between-group contact’ (ORC). The impact of this trait on the persistence of contagious pathogens that generate lifelong immunity in their hosts is currently unclear. We hypothesize that in populations with ORC, the formation, in groups, of a ‘protective barrier’ of only recovered adults, prevents the transmission of this type of pathogens to the new susceptible hosts (i.e. young animals), thereby increasing the probability of epidemic fade-out. We implement a spatially implicit individual-based Susceptible-Infected-Recovered (SIR) model for a large range of host and pathogen traits and show that the epidemic fade-out probability is consistently higher in populations with ORC, especially when disease spread is fast (high basic reproduction number R0). We also show that ORC can counteract the cost of group-living in terms of disease risk to a greater extent than variation in other traits. We discuss our findings in relation to herd immunity and outline how they could be used to implement efficient management measures such as vaccinations.


title: A reductive analysis of a compartmental model for COVID-19: data assimilation andforecasting for the United Kingdom

text: We introduce a deterministic model that partitions the total population into the susceptible, infected, quarantined, and those traced after exposure, recovered and the deceased. We introduce the concept of 'accessible population for transmission of the disease', which can be a small fraction of the total population, for instance when interventions are in force. This assumption, together with the structure of the set of coupled nonlinear ordinary differential equations for the populations, allows us to decouple the equations into just two equations. This further reduces to a logistic type of equation for the total infected population. The equation can be solved analytically and therefore allows for a clear interpretation of the growth and inhibiting factors in terms of the parameters in the full model. The validity of the 'accessible population' assumption and the efficacy of the reduced logistic model is demonstrated by the ease of fitting the United Kingdom data for the total number of infected cases. The model can also be used to forecast further progression of the disease. The approach further helps us to analyze the original model equations. We show that the original model equations provide a very good fit with the United Kingdom data for the cumulative number of infections. The active infected population of the model is seen to exhibit a turning point around mid-May, suggesting the beginning of a slow-down in the spread of infections. However, the rate of slowing down beyond the turning point is small and therefore the cumulative number of infections is likely to saturate to about 3.8 x 105 only towards the end of July or beginning of August, provided the lock-down conditions continue to prevail. Noting that the fits obtained from the reduced logistic equation and the full model equations are equally good, the underlying causes for the limited forecasting ability of the reduced logistic equation is elucidated. The model and the procedure adopted here are expected to be useful in fitting the data for other countries and forecasting the progression of the disease.


title: Clinical Efficacy of Intravenous Immunoglobulin Therapy in Critical Patients with COVID-19: A multicenter retrospective cohort study

text: Summary Background Coronavirus disease 2019 (COVID-19) has spread all over the world, causing more than 1.5 million infections and over ten thousands of deaths in a short period of time. However, little is known about its pathological mechanism, and there are still no clinical study reports on specific treatment. The purpose of this study is to determine the clinical efficacy of intravenous immunoglobulin (IVIG) therapy on COVID-19. Methods In this multicenter retrospective cohort study, adult critical COVID-19 patients (including severe type and critical type, according to the clinical classification defined by National Health Commission of China) in 8 government designated treatment center in China from Dec 23, 2019 to Mar 31, 2020 were enrolled. Demographic, clinical, treatment, and laboratory data, prognosis were extracted from electronic medical records, and IVIG was exposure factor. Primary outcomes were the 28 days and 60 days mortality, and secondary outcomes were the total length of in-hospital and the total duration of the disease. Meanwhile, the parameters of inflammation response and organ function were detected. The risk factors were determined by COX proportional hazards model. The subgroup analysis was carried out according to clinical classification of COVID-19, IVIG dosage and timing. Findings 325patients were included in this study, of whom 222 (68%) were severe type, 103 (32%) were critical type. 42 (13%) died in 28 days within hospitalization, total 54 (17%) died in 60 days, and 6 (3%) died in severe type, 48 (47%) died in critical type. 174 cases were used IVIG, and 151 cases were not. Compared with the baseline characteristics between two groups, the results showed that the patients in IVIG group had higher Acute Physiology and Chronic Health Evaluation (APACHII) score, Sequential Organ Failure Assessment (SOFA) score, IL-6 and lactate level, lower lymphocyte count and oxygenation index (all P<0.05). The 28 day and 60 day mortality did not improve with IVIG in overall patients. The in-hospital stay and the total duration of disease were longer in IVIG group (p<0.001). Risk factors were clinical classification (hazards ratio 0.126, 95% confidence interval 0.039-0.413, P=0.001), and using IVIG (hazards ratio 0.252, 95% confidence interval 0.107-0.591, P=0.002) with COX regression. Subgroup analysis showed that only in patients with critical type, IVIG could significantly reduce the 28 day mortality, decrease the inflammatory response and improve some organ functions (all p<0.05), and 60-day mortality reduced significantly by using IVIG in the early stage (admission[≤]7 days) and with high dose (>15 g/d). Interpretation Early and high dose of IVIG therapy may improve the prognosis of COVID-19 patients only in critical type, which provides the clinical basis for the choice of treatment population and method of IVIG therapy for the SARS-CoV-2 infection. Keywords: SARS-COV-2, COVID-19, IVIG, clinical efficacy, mortality


title: The comparative superiority of IgM-IgG antibody test to real-time reverse transcriptase PCR detection for SARS-CoV-2 infection diagnosis

text: Background: As the increasing number of Corona Virus Disease 2019 (COVID-19) patients caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2), which caused an outbreak initiated from Wuhan, China in December, 2019, the clinical features and treatment of COVID-19 patients have been understood. However, it is urgent to need the rapid and accurate detection for SARS-CoV-2 infection diagnosis. We aimed to evaluate the antibodies-based and nucleic acid-based tests (NAT) for SARS-CoV-2-infected patients. Method: We retrospectively and observationally studied 133 patients diagnosed with SARS-CoV-2 and admitted in Renmin Hospital of Wuhan University, China, from Feb 17 to Mar 1, 2020. Demographic data, symptoms, clinical examination, laboratory tests, and clinical outcomes were collected. Data were compared between IgM-IgG antibody test and real-time RT-PCR detection for COVID-19 patients. Results: Of 133 patients with SARS-CoV-2 infection, there were 44 moderate cases, 52 severe cases, and 37 critical cases with no significant difference of gender and age among three subgroups. Overall, the positive ratio in IgM antibody test was higher than in RT-PCR detection. In RT-PCR detection, the positive ratio was 65.91%, 71.15%, and 67.57% in moderate, severe, and critical cases, respectively. Whereas, the positive ratio of IgM/IgG antibody detection in patients was 79.55%/93.18%, 82.69%/100%, and 72.97%/97.30% in moderate, severe, and critical cases, respectively. Moreover, the concentrations of antibodies were also measured in three subgroups. Conclusion: The IgM-IgG antibodies-based test exhibited a comparative superiority to the NAT for COVID-19 diagnosis, which provides an effective complement to the false negative results from NAT for SARS-CoV-2 infection diagnosis.


title: Exploring diseases/traits and blood proteins causally related to expression of ACE2, the putative receptor of 2019-nCov: A Mendelian Randomization analysis

text: The novel coronavirus 2019-nCoV has caused major outbreaks in many parts of the world. A better understanding of the pathophysiology of COVID-19 is urgently needed. Clinically, it is important to identify who may be susceptible to infection and identify treatments for the disease. There is good evidence that ACE2 is a receptor for 2019-nCoV, and studies also suggested that high expression of ACE2 may increase susceptibility to infection. Here we conducted a phenome-wide Mendelian randomization (MR) study to prioritize diseases/traits and blood proteins that may be causally linked to ACE2 expression in the lung. Expression data was based on GTEx. We also explored drug candidates whose targets overlapped with the top-ranked proteins in MR analysis, as these drugs could potentially alter ACE2 expression and may be clinically relevant. Notably, MR is much less vulnerable to confounding and reverse causality compared to observational studies. The most consistent finding was a tentative causal association between diabetes-related traits and increased ACE2 expression. Based on one of the largest GWAS on type II diabetes (T2DM) to date (N=898,130), we found that T2DM is causally linked to raised ACE2 expression (beta=0.1835, 95% CI 0.0853-0.2817; p=2.49E-4; GSMR method). Significant associations (at nominal level; p<0.05) was also observed across multiple datasets, with different analytic methods, and for both type I and II diabetes. Other diseases/traits having nominal significant associations with increased ACE2 included inflammatory bowel disease, (ER+) breast and lung cancers, asthma, smoking and elevated ALT, among others. We also uncovered a number of plasma/serum proteins potentially linked to altered ACE2 expression, and the top enriched pathways included cytokine-cytokine-receptor interaction, VEGF signaling, JAK-STAT signaling etc. We also explored drugs that target some of the top-ranked proteins in the MR analysis. In conclusion, the current MR analysis reveals diseases/traits and blood proteins that may causally affect ACE2 expression, which in turn may influence susceptibility to the infection. The proteome-wide MR analysis may shed light on the molecular mechanisms underlying ACE2 expression, and may help guide drug repositioning in the future. Nevertheless, we stress that further studies are required to verify our findings due to various limitations and the exploratory nature of some analyses.


docid: hadnxjeo

title: Weather variables impact on COVID-19 incidence

text: We test the hypothesis of COVID-19 contagion being influenced by meteorological parameters such as temperature or humidity. We analysed data at high spatial resolution (regions in Italy and counties in the USA) and found that while at low resolution this might seem the case, at higher resolution no correlation is found. Our results are consistent with a poor outdoors transmission of the disease. However, a possible indirect correlation between good weather and a decrease in disease spread may occur, as people spend longer time outdoors.


title: Covid-19 - Knowledge, attitude and practice among medical and non-medical university students in Jordan

text: The World Health Organization declared COVID-19 as a pandemic on the 11thof March 2020. Since then, many efforts are being carried out to contain the virus. Knowledge and attitude of people should be directed towards strict preventive practices in order to halt the spread of the virus. The aim of the current cross-sectional study is to assess the knowledge, practice and attitude of university students from medical and non-medical colleges in Jordan using a structured questionnaire involving a total number of 592 students. A positive response regarding the overall knowledge about the symptoms of COVID-19 was observed in more than 90% of the students. In response to the attitude and practice, a good number of students nearly 99.7% agreed that hand washing is necessary for prevention of infection whereas 68.4% believed that mask wearing would prevent the infection. Around 6-7% students considered the virus as a stigma hence would not visit hospital. Also, around 10% students believed that their religious beliefs and body immunity might protect them from infection. More dangerously, 20.6% and 19.2% students believed antibiotics and smoking to be a protective measure against the infection respectively. Also, 96.8% do avoid hand shaking, 98.8% wash their hands and 93.3% use alcoholic rub, 95.8% cough or sneeze in a tissue and dispose it in waste bin, 51% will drink ginger with honey and 42.7% eat garlic for infection prevention. The main sources of knowledge were social media, internet and television. No significant difference was noticed between medical and non medical colleges. Thus, there is a need for more detailed and directed measures and awareness campaigns to improve the knowledge, attitude and practice in some critical aspects to contain the virus.


docid: cvqgtpbw

title: Dual nature of human ACE2 glycosylation in binding to SARS-CoV-2 spike

text: Binding of the spike protein of SARS-CoV-2 to the human angiotensin converting enzyme 2 (ACE2) receptor triggers translocation of the virus into cells. Both the ACE2 receptor and the spike protein are heavily glycosylated, including at sites near their binding interface. We built fully glycosylated models of the ACE2 receptor bound to the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. Using atomistic molecular dynamics (MD) simulations, we found that the glycosylation of the human ACE2 receptor contributes substantially to the binding of the virus. Interestingly, the glycans at two glycosylation sites, N90 and N322, have opposite effects on spike protein binding. The glycan at the N90 site partly covers the binding interface of the spike RBD. Therefore, this glycan can interfere with the binding of the spike protein and protect against docking of the virus to the cell. By contrast, the glycan at the N322 site interacts tightly with the RBD of the ACE2-bound spike protein and strengthens the complex. Remarkably, the N322 glycan binds into a conserved region of the spike protein identified previously as a cryptic epitope for a neutralizing antibody. By mapping the glycan binding sites, our MD simulations aid in the targeted development of neutralizing antibodies and SARS-CoV-2 fusion inhibitors.


title: Convalescent Plasma for COVID-19. A randomized clinical trial

text: Background After recovery from COVID-19, most patients have anti-SARS-CoV-2 neutralizing antibodies. Their convalescent plasma could be an inexpensive and widely available treatment for COVID-19. Methods The Convalescent-plasma-for-COVID (ConCOVID) study was a randomized trial comparing convalescent plasma with standard of care therapy in patients hospitalized for COVID-19 in the Netherlands. Patients were randomized 1:1 and received 300ml of plasma with anti-SARS-CoV-2 neutralizing antibody titers of at least 1:80. The primary endpoint was day-60 mortality and key secondary endpoints were hospital stay and WHO 8-point disease severity scale improvement on day 15. Results The trial was halted prematurely after 86 patients were enrolled. Although symptomatic for only 10 days (IQR 6-15) at the time of inclusion, 53 of 66 patients tested had anti-SARS-CoV-2 antibodies at baseline. A SARS-CoV-2 plaque reduction neutralization test showed neutralizing antibodies in 44 of the 56 (79%) patients tested with median titers comparable to the 115 donors (1:160 vs 1:160, p=0.40). These observations caused concerns about the potential benefit of convalescent plasma in the study population and after discussion with the data safety monitoring board, the study was discontinued. No difference in mortality (p=0.95), hospital stay (p=0.68) or day-15 disease severity (p=0.58) was observed between plasma treated patients and patients on standard of care. Conclusion Most COVID-19 patients already have high neutralizing antibody titers at hospital admission. Screening for antibodies and prioritizing convalescent plasma to risk groups with recent symptom onset will be key to identify patients that may benefit from convalescent plasma. Clinicaltrials.gov: NCT04342182


title: Do Weather Temperature and Median-age affect COVID-19 Transmission?

text: It was observed that the coldest countries and the eldest in terms of median-age were most distressed by COVID-19 pandemic, while the warmest countries and that have younger-aged population were the least affected. Therefore, this study utilized the non-linear least squares method to estimate the impact of weather temperatures and median age on COVID-19 cases per million in thirty-nine countries divided into two groups. The first group composed of twenty-four countries that announced the first COVID-19 case in January 2020, while the second group contains fifteen countries that witnessed the pandemic for the first time in February of the same year. The study revealed some major findings, which are: COVID-19 cases per million were not significantly affected by weather temperature or the median age in “January-group” countries (after 72.67 days on average), while COVID-19 cases per million increased significantly by decreasing temperatures, and increasing the median age in case of “February-group” countries (after an average of 44.80 days). This means that weather temperature and median age may influence the transmission rates of COVID-19 in its early stages, while weather temperature or median age no longer have effects in the advanced stages of the pandemic.


title: The Clinical Characteristics and Prognosis Factors of Mild-Moderate Patients With COVID-19 in a Mobile Cabin Hospital: A Retrospective, Single-Center Study

text: Background: Novel mobile cabin hospitals have been built to provide more makeshift beds for patients with COVID-19 in Wuhan. However, the characteristics of these patients needed be further described. Methods: This was a retrospective, single-center study. A total of 869 patients with confirmed COVID-19 were admitted to Wuchang Mobile Cabin Hospital in Wuhan, between February 6th, 2020 and February 20th, 2020. The final date of follow-up was March 6th, 2020. Clinical characteristics and outcome data were collected and analyzed. Results: Of 869 patients, the median age was 51 years (IQR, 40–58 years), and 377 patients (377/869; 43.4%) were men. A total of 616 patients (616/869; 70.9%) were discharged, 95 patients (95/869; 10.9%) were transferred to the designated hospital due to worsening condition (endpoint), and 158 patients (158/869; 18.2%) were still in the hospital. The incidence of the main symptoms, including fever, cough, fatigue, muscle aches, and anorexia, decreased with time. However, there were no differences in outcome among the patients with different onset times. Generally, both patients aged 45 years or older and patients with comorbidities were more likely to reach the endpoint (transfer to designated high-level hospitals due to condition worsen). In the other model, patients with the lung CT feature (e.g., ground-glass opacity, reticular/linear, air bronchogram, or consolidation shadow) were more likely to reach the endpoint. Conclusion: Older age, comorbidity, special chest CT features (e.g., ground-glass opacity, reticular/linear, air bronchogram, or consolidation shadow) are associated with poor prognosis for mild-moderate patients. The initial symptoms of mild-moderate patients may become insidious, which deserves our attention.


title: COVID-19 and Liver Dysfunction: Current Insights and Emergent Therapeutic Strategies

text: The outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has attracted increasing worldwide attention. Cases of liver damage or dysfunction (mainly characterized by moderately elevated serum aspartate aminotransferase levels) have been reported among patients with COVID-19. However, it is currently uncertain whether the COVID-19-related liver damage/dysfunction is due mainly to the viral infection per se or other coexisting conditions, such as the use of potentially hepatotoxic drugs and the coexistence of systemic inflammatory response, respiratory distress syndrome-induced hypoxia, and multiple organ dysfunction. Based on the current evidence from case reports and case series, this review article focuses on the demographic and clinical characteristics, potential mechanisms, and treatment options for COVID-19-related liver dysfunction. This review also describes the geographical and demographic distribution of COVID-19-related liver dysfunction, as well as possible underlying mechanisms linking COVID-19 to liver dysfunction, in order to facilitate future drug development, prevention, and control measures for COVID-19.


How to cite this article: Bhartiya S. Current Glaucoma Practice: The Covid-19 Impact. J Curr Glaucoma Pract 2020;14(1):1–2.


title: Children and the COVID-19 transition: Psychological reflections and suggestions on adapting to the emergency

text: The current period of transition due to COVID-19 emergency may negatively affect the psychological functioning of children and require resources aimed at supporting post-transition adaptation. Few contributions exist which specifically focus on what to do in such circumstances in order to assist the mental health of both children and parents. It seems therefore critical to provide strategies, which support the adjustment of children during the pre-existing and post-transition periods. Furthermore, screening projects are required in order to identify those children with increased levels of emotional and behavioural issues, beyond the COVID-19 transition, in order to plan specific interventions.


title: Politics and Science_ The Case of China and the Coronavirus

text: The Coronavirus (2019-nCoV, or COVID-19) outbreak started in the central Hubei province in China. The spread of the disease across China, and now around the globe, is a multi-layered issue that affects both politics and science. On one level, it is a public health crisis in an area where developing China is particularly vulnerable. On another, it sheds light on the issue of governance under Xi Jinping and the strengths and weaknesses of his highly centralised style of rule in contemporary China. Finally, it also speaks to the current atmosphere in geopolitics, where the boundary between China and the world around it, and particularly with the USA, is growing deeper. This article will look at each of these issues in turn. The spread and global impact of the virus has proved to be a fast-moving phenomenon. It is likely to make an impact that will last not just for years, but decades. There is every possibility that globalisation will be recast and reformed, as a result. This is a very initial attempt to understand some of the factors that might go into this, as they can be seen at the time of writing (April 2020).


title: Evaluating features of scientific conferences: A call for improvements

text: Scientific conferences provide valuable opportunities for researchers across career stages and disciplines to present their latest work and to network with their peers. The advent of the internet has opened new possibilities for interaction, collaboration and networking, yet the uptake of tools enabling remote participation at scientific meetings has been slow. Academic conferences have become more international with high proliferation in the number of meetings and attendees, but the format and quality of their organization lags behind what is possible. As a result, the experience of attending conferences in many disciplines today is not appreciably different in many respects. A few conferences in some disciplines have recently implemented valuable changes for the community and have become more receptive to attendees with families. Many meetings could still be improved significantly in terms of diversity, inclusivity, promoting early career researcher (ECR) networking and career development, venue accessibility, and more importantly, reducing the meetings’ carbon footprint. These issues are openly visible and to some extent discussed among researchers on social media. It is important to accelerate and mandate these efforts so that researchers in all disciplines, in particular ECRs, consistently benefit from scientific gatherings, for years to come. We examined the current state of over 260 national and international academic meetings in various disciplines for features of inclusivity and sustainability and propose solutions to make conferences more modern, effective, equitable and intellectually productive for the research community and environmentally sustainable for our planet. “They always say time changes things, but you actually have to change them yourself.” — Andy Warhol


docid: fjflzjxc

title: ‘A monstrous threat’: how a state of exception turns into a ‘new normal’

text: This article explores the factors that helped COVID-19 to become a ‘monstrous threat’ to humanity, which legitimises significant restrictions to people’s freedom and is justified by the ethics to keep everyone safe It analyses how rigid means increase old inequalities and produce secondary risks and significant side-effects and demonstrates how, with social and economic costs soaring, governments seek ways back – not to the old normal – but new social practices and attitudes towards infectious diseases, thereby transforming the state of exception into a ‘new normal’


title: Reduction of lymphocyte at early stage elevates severity and death risk of COVID-19 patients: a hospital-based case-cohort study

text: Background and objective: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced coronavirus disease 2019 (COVID-19) has been pandemic worldwide. Several reports observed a reduction of lymphocytes among COVID-19 patients. However, clinical significance of lymphocyte reduction in COVID-19 patients remains unclear. The objective of this study was to analyze the association between lymphocyte reduction at early stage and the prognosis of COVID-19 patients. Methods: All 192 hospitalized patients with COVID-19 were enrolled. Electronic medical records, including demographic data, clinical characteristics, comorbidities and exposure history, were collected. Biochemical indexes on admission and chest computed tomography (CT) were detected. Patient's prognosis was followed up. Results: On admission, 84 (43.8%) patients suffered from lymphocyte reduction among COVID-19 patients. The count and percentage of lymphocytes on admission were lower among more than seventy-year-old patients than those of younger patients. Multivariate logistic regression revealed that older age was a risk factor of lymphocyte reduction. Of interest, chest CT score, a key marker of lung injury, was increased among COVID-19 patients with lymphocyte reduction. By contrast, PaCO2, SpO2 and oxygenation index, several respiratory function markers, were decreased in COVID-19 patients with lymphocyte reduction. Moreover, TBIL and DBIL, two markers of hepatic injury, creatinine and urea nitrogen, two indices of renal function, and creatine kinase, AST and LDH, three myocardial enzymes, were elevated in COVID-19 patients with lymphocyte reduction. Among 84 COVID-19 patients with lymphocyte reduction, 32.1% died. Fatality rate was obviously higher in COVID-19 patients with lymphocyte reduction than those with normal lymphocyte (RR=5.789, P<0.001). Conclusion: Older COVID-19 patients are more susceptible to lymphocyte reduction. Lymphocyte reduction at early stage aggravates the severity of multiple organ injuries and elevates death risk of COVID-19 patients.


title: The BathRC model: a method to estimate flow restrictor size for dual ventilation of dissimilar patients

text: With large numbers of COVID-19 patients requiring mechanical ventilation and ventilators being in short supply, in extremis two patients are having to share one ventilator. This possibility has been discussed for at least two decades, and careful matching of patient ventilation requirements is advised. However, with a large range of lung compliance and other characteristics, which may also vary with time, good matching is difficult to achieve. Adjusting the impedance of the flow path between ventilator and patient gives the opportunity to control the airway pressure and hence flow and volume individually for each patient. Several groups are now investigating this, in particular the addition of a flow restrictor in the inspiration tube for the patient who is more compliant, or requires a lower tidal volume. In this paper, we show that a simple linear resistance-compliance model, termed the BathRC model, of the ventilator tubing system and lung allows direct calculation of the relationships between pressures, volumes, and required flow restriction. The BathRC model is experimentally validated using a GE Aisys CS2 ventilator connected to two test lungs. The pressure-flow relationships for two restrictors are experimentally determined, and despite the need to approximate them with a linear resistance characteristic, their effect in the breathing circuit is accurately predicted by the simple model. The BathRC model is freely available for download; we do not condone dual ventilation, but this tool is provided to demonstrate that flow restriction can be readily estimated. This research is part of a larger test, simulation and design investigation on dual ventilation being undertaken at the UoB and RUH.


title: COVID-19 challenges to dentistry in the new pandemic epicenter: Brazil

text: A nationwide survey of dentists was carried out in Brazil, a new pandemic epicenter, to analyze how dental coverage has been affected (public versus private networks), changes in routine and burdens, and how the local prevalence of COVID-19 affects dental professionals. Dentists were recruited via email and an Instagram campaign. Responses to an online questionnaire were collected May 15-24, 2020. COVID-19 case/death counts in the state where respondents work was used to test associations between contextual status and decreases in weekly appointments, fear of contracting COVID-19 at work, and current work status (alpha=0.05). Over 10 days, 3,122 responses were received, with region, gender, and age distributions similar to those of dentists in Brazil. Work status was affected for 94% of dentists, with less developed regions being more impacted. The impact on routine was high or very high for 84%, leading to varied changes to clinic infrastructure, personal protective equipment use, patient screening, and increased costs. COVID-19 patients had been seen by 5.3% of respondents, and 90% reported fearing contracting COVID-19 at work. Multilevel statistics showed that greater case and death rates (1000 cases or 100 deaths per million inhabitants) in one's state increased the odds of being fearful of contracting the disease (by 18% and 25%). For each additional 1000 cases or 100 deaths, the odds of currently not working or treating emergencies increased by 36% and 58%. The reduction in patients seen weekly per dentist was greater in public (38.7+/-18.6) than in private clinics (22.5+/-17.8). This study provides early evidence of three major impacts of the pandemic on dentistry in Brazil: increasing inequalities due to coverage differences between public and private networks; adoption of new clinical routines, which are associated with an economic burden; and associations of regional COVID-19 incidence and mortality with fear of contracting the disease at work.


title: A Sentinel COVID-19 Case in Houston, Texas: Informing Frontline Emergency Department Screening and Preparedness

text: Abstract In December 2019, a cluster of severe pneumonia cases of unknown cause was reported in Wuhan, Hubei province, China A novel strain of coronavirus belonging to the same family of viruses that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) was identified In February 2020, cases began being identified in the United States We describe a sentinel CoVID-19 patient in Houston,Texas, who first presented on March 1, 2020 The patient did not meet criteria for a Person Under Investigation (PUI) as recommended by the Centers for Disease Control (CDC) at the time This case has broad implications for emergency department screening and preparedness for CoVID-19 and other future infectious diseases This article is protected by copyright All rights reserved


title: Did pangolins spread the China coronavirus to people?

text: Genetic sequences of viruses isolated from the scaly animals are 99% similar to that of the circulating virus — but the work is yet to be formally published Genetic sequences of viruses isolated from the scaly animals are 99% similar to that of the circulating virus — but the work is yet to be formally published


docid: fnguelau

title: The SARS-CoV-2 receptor-binding domain elicits a potent neutralizing response without antibody-dependent enhancement

text: The SARS-coronavirus 2 (SARS-CoV-2) spike (S) protein mediates entry of SARS-CoV-2 into cells expressing the angiotensin-converting enzyme 2 (ACE2). The S protein engages ACE2 through its receptor-binding domain (RBD), an independently folded 197-amino acid fragment of the 1273-amino acid S-protein protomer. Antibodies to the RBD domain of SARS-CoV (SARS-CoV-1), a closely related coronavirus which emerged in 2002-2003, have been shown to potently neutralize SARS-CoV-1 S-protein-mediated entry, and the presence of anti-RBD antibodies correlates with neutralization in SARS-CoV-2 convalescent sera. Here we show that immunization with the SARS-CoV-2 RBD elicits a robust neutralizing antibody response in rodents, comparable to 100 µg/ml of ACE2-Ig, a potent SARS-CoV-2 entry inhibitor. Importantly, anti-sera from immunized animals did not mediate antibody-dependent enhancement (ADE) of S-protein-mediated entry under conditions in which Zika virus ADE was readily observed. These data suggest that an RBD-based vaccine for SARS-CoV-2 could be safe and effective.


title: MIGRANTS IN TRANSIT AND ASYLUM SEEKERS IN MEXICO: AN EPIDEMIOLOGICAL ANALYSIS OF THE COVID-19 PANDEMIC

text: BACKGROUND: Migrants could be disproportionately affected by the COVID-19 pandemic, yet little is known so far of the epidemiology of the disease among them, especially in low- and middle-income countries. OBJECTIVE: To describe the epidemiology of suspect cases of COVID-19 in migrants in transit and asylum seekers in Mexico, and to compare their characteristics with those of non-migrants. METHODS: This was a secondary analysis of information from the surveillance system of Mexico from January 1 to May 3 2020, identifying persons from the main sending countries of mixed migrant flows in Mexico (Central America, the Caribbean, Venezuela and African countries), in northern and southern Mexican border states. We compared the demographic and clinical characteristics, risk conditions, and epidemic curves for migrants and non-migrants. Also, we estimated the cumulative incidence for non-migrants, and for migrants in two scenarios defined by different estimations of their population size. RESULTS: Migrants were on average younger, had less accompanying risk conditions, and a lower percentage of suspect cases tested positive for COVID-19. The odds of hospitalization were lower among migrants, but the difference disappeared after adjusting by age, gender and underlying risk conditions. The cumulative incidence ratios comparing migrants with non-migrants were 6.12 (CI95% 4.75,7.77) for the first scenario, and 1.49 (CI95% 1.15,1.89) for the second scenario. CONCLUSION: Migrants and asylum seekers in Mexico are at increased risk for infectious respiratory diseases, and could be disproportionately affected by COVID-19. It is important to continue monitoring the situation, with more detailed information about migration status, living conditions and other determinants of migrants health.


Science Teacher Education in the Times of the COVID-19 Pandemic


title: Estimating the distance to an epidemic threshold

text: The epidemic threshold of the susceptible-infected-recovered (SIR) model is a boundary separating parameters that can permit epidemics from those that cannot. This threshold corresponds to points where the stability of the system’s equilibrium reaches zero. Consequently, we use the average rate at which deviations from the equilibrium shrink to define a distance to this threshold. However, the vital dynamics of the host population may occur slowly even when transmission is far from threshold levels. Here we show analytically how such slow dynamics can prevent estimation of the distance to the threshold for some individual variables of the model. Although these results are exact only in the limit of long-term observation of a large system, we find that they still provide useful insight into the behaviour of estimates from simulations with a range of population sizes, environmental noise, and observation schemes. Having established some guidelines about when estimates are accurate, we then illustrate how multiple distance estimates can be used to estimate the rate of approach to the threshold. The estimation approach is general and may be applicable to zoonotic pathogens such as MERS-CoV as well as vaccine-preventable diseases such as measles.


docid: zcktrmyg

title: Breaking the back of COVID-19: Is Bangladesh doing enough testing?

text: Following detection of the first 100 confirmed cases of COVID-19 in early April, Bangladesh stepped up its efforts to strengthen testing capacity in order to curb the spread of the disease across the country. This paper sheds light on the position of Bangladesh in relation to its South Asian neighbors India and Pakistan with respect to testing capacity and ability to detect cases with increased testing. It also analyzes recent data on case counts and testing numbers in Bangladesh, to provide an idea regarding the number of extra tests needed to detect a substantial number of cases within a short period of time. Findings indicate that compared to India and Pakistan, Bangladesh was able to detect more cases by increasing testing levels and expand its testing capacity by performing more per capita tests. In spite of these achievements, the rate of reported cases per 100 tests was consistently higher for Bangladesh compared to India, which suggests that in addition to increased testing, other factors, such as, effective enforcement of social distancing and efficient contact tracing are just as important in curbing the spread of the disease. The analysis reveals that current testing levels in Bangladesh are not adequate. Based on the findings, we recommend a 30-50% growth of the current test rate in the next few days so that by detecting and isolating more cases, Bangladesh could, in effect, contain the spread of new infections. The challenge, however, is to mobilize resources necessary to expand geographical coverage and improve testing quality while enforcing social distancing and performing efficient contact tracing.


title: Hypokalemia in Patients with COVID-19

text: Patients with COVID-19 may experience multiple conditions (e.g., fever, hyperventilation, anorexia, gastroenteritis, acid-base disorder) that may cause electrolyte imbalances. Hypokalemia is a concerning electrolyte disorder that may increase the susceptibility to various kinds of arrhythmia. This study aimed to estimate prevalence, risk factors and outcome of hypokalemia in a cohort of non-critically ill patients. A retrospective analysis was conducted on 290 hospitalized patients with confirmed COVID-19 infection at the tertiary teaching hospital of Modena, Italy. Hypokalemia (<3.5 mEq/L) was detected in 119 patients (41%). The decrease of serum potassium level was of mild entity (3-3.4 mEq/L) and occurred in association with hypocalcemia (P=0.001) and lower level of serum magnesium (P=0.028) compared to normokaliemic patients. Urine K: creatinine ratio, measured in a small subset of patients (n=45; 36.1%), showed an increase of urinary potassium excretion in the majority of the cases (95.5%). Causes of kaliuria were diuretic therapy (53.4%) and corticosteroids (23.3%). In the remaining patients, urinary potassium loss was associated with normal serum magnesium, low sodium excretion (FENa< 1%) and metabolic alkalosis. Risk factors for hypokalemia were female gender (P=0.002; HR 0.41, 95%CI 0.23-0.73) and diuretic therapy (P=0.027; HR 1.94, 95%CI 1.08-3.48). Hypokalemia, adjusted for sex, age and SOFA score, resulted not associated with ICU admission (P=0.131, 95% CI 0.228-1.212) and in-hospital mortality (P=0.474; 95% CI 0,170-1,324) in our cohort of patients. Hypokalemia is a frequent disorder in COVID-19 patients and urinary potassium loss may be the main cause of hypokalemia. The disorder was mild in the majority of the patients and was unrelated to poor outcomes. Nevertheless, hypokalemic patients required potassium supplements to dampen the risk of arrhythmias.


title: Linguistic (homo)nationalism, legitimacies, and authenticities in Singapore's Pink Dot discourse

text: Pink Dot SG is an LGBTQ social movement in Singapore, which since its inception in 2009 organizes an annual free-to-all public gathering in the Speaker's Corner at Hong Lim Park. Over the years, the gathering has grown in size, and has gained national and international visibility. Prior to the event each year, a set of official YouTube promotional videos is released on its website in order to announce the event and garner support for the movement and participation at the event. In this article, I examine the politics of language performances in the videos from 2009 to 2019, which seeks to blend social legitimacy and authenticity in strategic ways in achieving a ‘linguistic homonationalism’. Linguistic homonationalism, in this study, refers to the harnessing of language ideological choices to align with nationalistic values in the promotion of LGBTQ interests.


title: Untreated Stroke as Collateral Damage of COVID-19: “Time Is Brain” Versus “Stay at Home”

text: For decades, neurologists have been advocating that anyone with acute focal deficits report immediately to the closest hospital’s emergency room. Major advancements in the hyperacute diagnosis and treatment of stroke have justified our call-to-action slogan of “Time is Brain”—faster therapy leads to superior outcomes. However, this mantra has been recently usurped by the catchphrase “Stay at Home” during the coronavirus disease 2019 (COVID-19) pandemic. Fewer patients are presenting to hospitals with acute stroke; our census is down. Presumably the etiology of this phenomenon is either strict “social distancing” that some people may misperceive to exclude even emergent situations, or fears of contracting the virus while hospitalized. In this Short Report, we describe the year-over-year drop in stroke volume (ischemic and hemorrhagic both) coinciding with a paradoxical rise in acute reperfusion therapies at our university hospital. These data imply that stroke patients with mild/moderate symptoms are most likely staying home, and not receiving urgent therapies, and correspondingly, only the most severely disabled stroke patients are ultimately seeking and receiving help. We must remind our patients and the general public that our services are essential and available, as stroke still remains a medical emergency, and carries a likely higher overall mortality risk than COVID-19. As neurologists, we also must be vigilant for the atypical presentations and varied etiologies of stroke associated with COVID-19 as well.


title: How robust are the results of one of the first positive trials exploring hydroxychloroquine for treatment of COVID-19?

text: An outbreak of a novel human coronavirus infection emerged in Wuhan, China in December 2019. Two months later, the World Health Organization (WHO) announced SARS-CoV-2 as the name for the new virus and COVID-19 for the associated illness. On March 12, 2020, the WHO officially declared COVID-19 as a pandemic. The scientific community has raced to find effective therapeutic agents against the virus. Gautret et al 2020 is among one of the first purportedly positive trials of hydroxychloroquine for the treatment of COVID-19. However, it is imperative that a thorough analysis and understanding of trial data be undertaken prior to making claims about safety and efficacy. Our group assessed the statistical robustness of the trial using the Fragility Index (FI). The FI provides a numerical quantification of a clinical trial's conclusions. The index is based on iterative statistical calculations to determine the minimum number of events within a trial that would theoretically need to change from positive to negative in order for the trial's endpoint to convert from significant to non-significant; the higher the index, the more statistically robust the study results. For the Gautret et al trial, one endpoint had an FI of 1, two had indices of 2, and another had an index of 4. The primary endpoint of viral clearance on day 6 had an FI of 4. This indicates that if 4 events were to change from positive to negative, the conclusion of the trial would become mathematically non-significant. This index is comparable to many other published trials of established agents; the median FI across the reported literature appears to be 2. In conclusion, the trial results reported by Gautret et al are statistically robust, assuming that data quality is not compromised; however, the study was an open-label trial with non-homogenous groups, with analysis conducted per-protocol. Additionally, SARS-CoV-2 Reverse Transcriptase-PCR (RT-PCR) testing was not conducted in a systematic way amongst the two groups. Further analyses of this trial and future trials of antiviral agents with potential activity against SARS-CoV-2 should be performed with complementary epidemiologic and statistical techniques to determine whether the trial's results are clinically important and/or should be explored in depth. Given the statistically robust results reported by Gautret et al, despite the study's inherent methodological and analytical flaws, hydroxychloroquine should be studied as a potential agent against COVID-19 in larger clinical trials.


title: Anosmia and Ageusia as the Only Indicators of Coronavirus Disease 2019 (COVID-19)

text: The patient is a 60-year-old woman with a history of vertigo and seasonal allergies who presented to the hospital with the chief complaint of headache. Radiological findings were negative for intracranial abnormalities. The headache was due to trigeminal neuralgia. She had concurrent complaints of anosmia and ageusia without fever, respiratory symptoms, or obvious risk factors. However, it was determined to test the patient for coronavirus disease 2019 (COVID-19) infection despite extremely low clinical suspicion. Unfortunately, she was found to be COVID-19 positive after she was discharged from the hospital while she remained asymptomatic. There is currently a lack of published case reports describing COVID-19 patients with the sole symptoms of anosmia and ageusia in the United States of America.


title: Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study

text: Background: Coronavirus disease-2019 (COVID-19) is a rapidly escalating epidemic caused by SARS-CoV-2. Identification of a simple and effective indicator to assess disease severity and outcome is urgently needed. Methods: This study retrospectively analyzed dynamic changes of lymphocyte percentage (LYM%) in 15 death cases, 15 severe cases as well as 40 moderate cases of COVID-19 patients. Next, prognostic role of lymphopenia in COVID-19 were verified in 92 hospitalized cases. Results: Our results from death and severe cases showed that LYM% in blood test were inversely associated with the progression and severity of COVID-19. LYM% in patients with moderate COVID-19 remained higher than 20% 10-12 days after symptom onset. In contrast, LYM% was lower than 20% in severe cases. However, LYM% in severe cases was higher than 5% 17-19 days after the onset of the disease, while it fell below 5% in death cases. Therefore, we established a reliable Time from symptom onset-LYM% model (TLM), which could be used to evaluate disease severity and predict the outcomes of hospitalized patients with COVID-19. Conclusion: Lymphopenia can be used to indicate clinical course, treatment effect and outcomes of COVID-19 patients.


title: Hydroxychloroquine application is associated with a decreased mortality in critically ill patients with COVID-19

text: Importance: Coronavirus disease 2019 (COVID-19) is a pandemic with no specific drugs and high mortality. The most urgent thing is to find effective treatments. Objective: To determine whether hydroxychloroquine application may be associated with a decreased risk of death in critically ill COVID-19 patients and what is potential mechanism. Design, Setting and Patients: This retrospective study included all 568 critically ill COVID-19 patients who were confirmed by pathogen laboratory tests despite antiviral treatment and had severe acute respiratory distress syndrome, PAO2/FIO2 <300 with need of mechanical ventilation in Tongji Hospital, Wuhan, between February 1 of 2020 to April 8 of 2020. All 568 patients received comparable basic treatments including antiviral drugs and antibiotics, and 48 of them additionally received oral hydroxychloroquine (HCQ) treatment (200 mg twice a day for 7-10 days). Primary endpoint is mortality of patients, and inflammatory cytokines levels were compared between hydroxychloroquine and non-hydroxychloroquine (NHCQ) treatments. MAIN OUTCOMES AND MEASURES: In-hospital death and hospital stay time (day) were obtained, level of inflammatory cytokine (IL-6) was measured and compared between HCQ and NHCQ treatments. RESULTS: The median age of 568 critically ill patients is 68 (57, 76) years old with 37.0% being female. Mortalities are 18.8% (9/48) in HCQ group and 45.8% (238/520) in NHCQ group (p<0.001). The time of hospital stay before patient death is 15 (10-21) days and 8 (4 - 14) days for the HCQ and NHCQ groups, respectively (p<0.05). The level of inflammatory cytokine IL-6 was significantly lowered from 22.2 (8.3-118.9) pg/mL at the beginning of the treatment to 5.2 (3.0-23.4) pg/ml (p<0.05) at the end of the treatment in the HCQ group but there is no change in the NHCQ group. CONCLUSIONS AND RELEVANCE: Hydroxychloroquine treatment is significantly associated with a decreased mortality in critically ill patients with COVID-19 through attenuation of inflammatory cytokine storm. Therefore, hydroxychloroquine should be prescribed for treatment of critically ill COVID-19 patients to save lives.


title: More than privacy: Australians' concerns and misconceptions about the COVIDSafe App: a short report

text: This survey of 1500 Australians about the COVIDSafe app found that the reasons for not downloading included privacy concerns, phone capabilities, and beliefs of limited benefit. COVIDSafe knowledge varied with confusion about purpose and capabilities. Public health messaging will need to address these perceptions to achieve sufficient uptake.


title: COVID‐19 and online teaching in higher education: A case study of Peking University

text: Starting from the spring of 2020, the outbreak of the COVID‐19 caused Chinese universities to close the campuses and forced them to initiate online teaching. This paper focuses on a case of Peking University's online education. Six specific instructional strategies are presented to summarize current online teaching experiences for university instructors who might conduct online education in similar circumstances. The study concludes with five high‐impact principles for online education: (a) high relevance between online instructional design and student learning, (b) effective delivery on online instructional information, (c) adequate support provided by faculty and teaching assistants to students; (d) high‐quality participation to improve the breadth and depth of student's learning, and (e) contingency plan to deal with unexpected incidents of online education platforms.


title: Sustainable social distancing through facemask use and testing during the Covid-19 pandemic

text: We investigate how individual protective behaviors, different levels of testing, and isolation influence the transmission and control of the COVID-19 pandemic. Based on an SEIR-type model incorporating asymptomatic but infectious individuals (40%), we show that the pandemic may be readily controllable through a combination of testing, treatment if necessary, and self-isolation after testing positive (TTI) of symptomatic individuals together with social protection (e.g., facemask use, handwashing). When the basic reproduction number, R0, is 2.4, 65% effective social protection alone (35% of the unprotected transmission) brings the R below 1. Alternatively, 20% effective social protection brings the reproduction number below 1.0 so long as 75% of the symptomatic population is covered by TTI within 12 hours of symptom onset. Even with 20% effective social protection, TTI of 1 in 4 symptomatic individuals can substantially 'flatten the curve' cutting the peak daily incidence in half.


title: The respiratory sound features of COVID-19 patients fill gaps between clinical data and screening methods

text: Background: The 2019 novel coronavirus (COVID-19) has continuous outbreaks around the world. Lung is the main organ that be involved. There is a lack of clinical data on the respiratory sounds of COVID-19 infected pneumonia, which includes invaluable information concerning physiology and pathology. The medical resources are insufficient, which are now mainly supplied for the severe patients. The development of a convenient and effective screening method for mild or asymptomatic suspicious patients is highly demanded. Methods: This is a retrospective case series study. 10 patients with positive results of nucleic acid were enrolled in this study. Lung auscultation was performed by the same physician on admission using a hand-held portable electronic stethoscope delivered in real time via Bluetooth. The recorded audio was exported, and was analyzed by six physicians. Each physician individually described the abnormal breathing sounds that he heard. The results were analyzed in combination with clinical data. Signal analysis was used to quantitatively describe the most common abnormal respiratory sounds. Results: All patients were found abnormal breath sounds at least by 3 physicians, and one patient by all physicians. Cackles, asymmetrical vocal resonance and indistinguishable murmurs are the most common abnormal breath sounds. One asymptomatic patient was found vocal resonance, and the result was correspondence with radiographic computed tomography. Signal analysis verified the credibility of the above abnormal breath sounds. Conclusions: This study describes respiratory sounds of patients with COVID-19, which fills up for the lack of clinical data and provides a simple screening method for suspected patients.


title: Search for asymptomatic carriers of SARS-CoV-2 in healthcare workers during the pandemic: a Spanish experience

text: Objective: determine the percentage of healthcare workers (HCW) carrying SARS-CoV-2 in high exposure areas of the hospital. Design: cross- sectional study during April 15-24th in Hospital Costa del Sol (Marbella, Spain), excluding HCW with previous COVID19. Setting: hospital based, focused on patient care areas COVID19. Participants: 498 subjects, 80% women. Participation was offered to all the HCW of Emergencies, Intensive Care and Anesthesia, Internal Medicine and Pneumology. Other units not directly involved in the care of these patients were offered to participate. Intervention: naso and oropharyngeal PCR determination was performed together with IgG and IgM antibody determination by immunochromatography. On the day of sampling, a health questionnaire was answered, reporting symptoms on the same day and in the previous fourteen days. Main outcome measures: percentage of HCW with positive PCR for SARS-CoV-2, percentage of HCW with positive IgG for SARS-CoV-2. Results: Two individuals were detected with PCR for SARS-CoV-2 positive (0.4%). Both were asymptomatic on the day of sampling, but one of them had had a CoVID-19 compatible picture in the previous two weeks and had positive IgG and IgM; therefore, only one subject was truly asymptomatic carrier (0.2%). 9 workers with positive IgG (1.8%) were detected. Conclusions: the prevalence of asymptomatic carriers among health workers of the services directly involved in the care of patients with CoVID-19 was very low in our center. This type of strategy can be one more tool in controlling the pandemic.


title: Rapid direct nucleic acid amplification test without RNA extraction for SARS-CoV-2 using a portable PCR thermocycler

text: There is an ongoing worldwide coronavirus disease 2019 (Covid-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). At present, confirmatory diagnosis is by reverse transcription polymerase chain reaction (RT-PCR), typically taking several hours and requiring a molecular laboratory to perform. There is an urgent need for rapid, simplified and cost-effective detection methods. We have developed and analytically validated a protocol for direct rapid extraction-free PCR (DIRECT-PCR) detection of SARS-CoV-2 without the need for nucleic acid purification. As few as 6 RNA copies per reaction of viral nucleocapsid (N) gene from respiratory samples such as sputum and nasal exudate can be detected directly using our one-step inhibitor-resistant assay. The performance of this assay was validated on a commercially available portable PCR thermocycler. Viral lysis, reverse transcription, amplification and detection are achieved in a single-tube homogeneous reaction within 36 minutes. This minimized hands-on time, reduces turnaround-time for sample-to-result and obviates the need for RNA purification reagents. It could enable wider use of Covid-19 testing for diagnosis, screening and research in countries and regions where laboratory capabilities are limiting.


title: Application and optimization of RT-PCR in diagnosis of SARS-CoV-2 infection

text: Background: Coronavirus Disease 2019 (COVID-19) caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global threat to public health. Aiming to construct an efficient screening pattern, we comprehensively evaluated the performances of RT-PCR and chest CT in diagnosing COVID-19. Methods: The records including demographics, RT-PCR, and CT from 87 confirmed COVID-19 cases and 481 exclusion cases were collected. The diagnostic accuracy of the pharyngeal swab RT-PCR, CT, combination with the second pharyngeal swab RT-PCR or with CT were evaluated individually. Besides, all the stool RT-PCR results were plotted by time to explore the value of stool RT-PCR. Findings: Combination of RT-PCR and CT has the higher sensitivity (91.9%,79/86) than RT-PCR alone (78.2%，68/87) or CT alone (66.7%, 54 of 81) or combination of two RT-PCR tests (86.2%,75/87). There was good agreement between RT-PCR and CT (kappa-value, 0.430). In 34 COVID-19 cases with inconsistent results, 94.1% (n=32) are mild infection, 62.5% of which (20/32) showed positive RT-PCR. 46.7% (35/75) COVID-19 patients had at least one positive stool during the course. Two cases had positive stool earlier than the pharyngeal swabs. Importantly, one patient had consecutive positive stool but negative pharyngeal swabs. Interpretation: Combination of RT-PCR and CT with the highest sensitivity is an optimal pattern to screen COVID-19. RT-PCR is superior to CT in diagnosing mild infections. Stool RT-PCR should be considered as an item for improving discovery rate and hospital discharge. This study shed light for optimizing scheme of screening and monitoring of SARS-CoV-2 infection.


title: BCG is a good immunotherapeutic agent for viral and autoimmune diseases: Is it a new weapon against coronavirus (COVID-19)?

text: Now nearly a century old, the Bacillus Calmette-Guérin (BCG) vaccine is used routinely in humans for the prophylaxis of tuberculosis and to clear up leprosy. As the immune response to the vaccine shows some degree of cross-antigenicity, the vaccine also affects a level of resistance to a range of unrelated diseases and pathogens. Clinical studies data have shown that the BCG vaccine has effects on autoimmune and inflammatory diseases. Although the vaccine does not possess any inherent antiviral activity, it engages in the host immune system such that many types of viral infections are considerably reduced. Hence, we expect that the frequency and severity of many microbial diseases, including COVID-19, will be lower in counties in which mass BCG vaccination programs are implemented. So the BCG vaccine may prove useful in the coming months especially in countries where already have mass BCG vaccination, as the COVID-19 pandemic has placed an unprecedented strain on health services across the world. Currently, countless front-line healthcare staff is in immediate danger of exposure to the SARS-CoV-2 virus. Furthermore, as oral zinc sulfate as immunomodulator has proved an effective means to treat various viral diseases (including viral warts and herpes), parasitic infections, and diseases with autoimmune reactions such as Behcet’s disease and recurrent aphthous stomatitis, it could be employed in combination with the BCG vaccine to enhance the immunological functions of patients with COVID-19. So BCG immunotherapy combined with oral zinc sulfate will be encouraging protective programs in societies where coronavirus is going to spread.