title: Geographical Variation in COVID-19 Cases, Prevalence, Recovery and Fatality Rate by Phase of National Lockdown in India, March 14-May 29, 2020

text: Background: Since the COVID-19 pandemic hit Indian states at varying speed, it is crucial to investigate the geographical pattern in COVID-19. We analyzed the geographical pattern of COVID-19 prevalence and mortality by the phase of national lockdown in India. Method: Using publicly available compiled data on COVID-19, we estimated the trends in new cases, period-prevalence rate (PPR), case recovery rate (CRR), and case fatality ratio (CFR) at national, state and district level. Findings: The age and sex are missing for more than 60 percent of the COVID-19 patients. There is an exponential increase in COVID-19 cases both at national and sub-national levels. The COVID-19 infected has jumped about 235 times ( from 567 cases in the pre-lockdown period to 1,33,669 in the fourth lockdown); the average daily new cases have increased from 57 in the first lockdown to 6,482 in the fourth lockdown; the average daily recovered persons from 4 to 3,819; the average daily death from 1 to 163. From first to the third lockdown, PPR (0.04 to 5.94), CRR (7.05 to 30.35) and CFR (1.76 to 1.89) have consistently escalated. At state-level, the maximum number of COVID-19 cases is found in the states of Maharashtra, Tamil Nadu, Delhi, and Gujarat contributing 66.75 percent of total cases. Whereas no cases found in some states, Kerela is the only state flattening the COVID-19 curve. The PPR is found to be highest in Delhi, followed by Maharastra. The highest recovery rate is observed in Kerala, till second lockdown; and in Andhra Pradesh in third lockdown. The highest case fatality ratio in the fourth lockdown is observed in Gujarat and Telangana. A few districts viz. like Mumbai (96.7); Chennai (63.66) and Ahmedabad (62.04) have the highest infection rate per 100 thousand population. Spatial analysis shows that clusters in Konkan coast especially in Maharashtra (Palghar, Mumbai, Thane and Pune); southern part from Tamil Nadu (Chennai, Chengalpattu and Thiruvallur), and the northern part of Jammu & Kashmir (Anantnag, Kulgam) are hot-spots for COVID-19 infection while central, northern and north-eastern regions of India are the cold-spots. Conclusion: India has been experiencing a rapid increase of COVID-19 cases since the second lockdown phase. There is huge geographical variation in COVID-19 pandemic with a concentration in some major cities and states while disaggregated data at local levels allows understanding the geographical disparity of the pandemic, the lack of age-sex information of the COVID-19 patients forbids to investigate the individual pattern of COVID-19 burden. Keyword: COVID-19; India; Case Fatality Rate; Case Recovery Rate; Period Prevalence Rate; Geographical variation


title: Coronavirus, as a source of pandemic pathogens

text: The coronavirus and the influenza virus have similarities and differences. In order to comprehensively compare them, their genome sequencing data were examined by principal component analysis. Variations in coronavirus were smaller than those in a subclass of the influenza virus. In addition, differences among coronaviruses in a variety of hosts were small. These characteristics may have facilitated the infection of different hosts. Although many of the coronaviruses were more conservative, those repeatedly found among humans showed annual changes. If SARS-CoV-2 changes its genome like the Influenza H type, it will repeatedly spread every few years. In addition, the coronavirus family has many other candidates for subsequent pandemics. One Sentence Summary The genome data of coronavirus were compared to influenza virus, to investigate its spreading mechanism and future status. Coronavirus would repeatedly spread every few years. In addition, the coronavirus family has many other candidates for subsequent pandemics.


title: QMRA of SARS-CoV-2 for workers in wastewater treatment plants

text: Faecal-oral transmission of SARS-CoV-2 is a hot topic and additional research is needed to elucidate the risks of the novel coronavirus in sanitation systems. This is the first article that investigates the potential health risks of SARS-CoV-2 in sewage to wastewater treatment plants (WWTPs) workers. A quantitative microbial risk assessment (QMRA) is applied for three COVID-19 scenarios (moderate, aggressive and extreme) to study the effect of different stages of the pandemic, in terms of percentage of infected population, on the probability of infection. Results reveal that estimates of viral loads in sewage at the entrance of WWTPs ranged from 1.03x102 to 1.31x104 GC.mL-1 (0.1 to 13.06 PFU.mL-1, respectively) and that estimated risks for the aggressive and extreme scenarios (6.5x10-3 and 3.1x10-2, respectively) were likely to be above a WHO benchmark of tolerable risk used for virus infection of 10-3 and higher than the risk of infection of E. coli, used herein as common pathogen indicator for a relative comparison, thus reinforcing the concern of sewage systems as a transmission pathway of SARS-CoV-2. These findings are helpful as an early-warning tool and in prioritizing upcoming risk management strategies in the sanitation sector during COVID-19 pandemic.


title: Patient DNA cross-reactivity of the CDC SARS-CoV-2 extraction control leads to an inherent potential for false negative results

text: Testing for RNA viruses such as SARS-CoV-2 requires careful handling of inherently labile RNA during sample collection, clinical processing, and molecular analysis. Tests must include fail-safe controls that affirmatively report the presence of intact RNA and demonstrate success of all steps of the assay. A result of “no virus signal” is insufficient for clinical interpretation: controls must also say “The reaction worked as intended and would have found virus if present.” Unfortunately, a widely used test specified by the US Centers for Disease Control and Prevention (CDC) incorporates a control that does not perform as intended and claimed. Detecting SARS-CoV-2 with this assay requires both intact RNA and successful reverse transcription. The CDC-specified control does not require either of these, due to its inability to differentiate human genomic DNA from reverse-transcribed RNA. Patient DNA is copurified from nasopharyngeal swabs during clinically-approved RNA extraction and is sufficient to return an “extraction control success” signal using the CDC design. As such, this assay fails-unsafe: truly positive patient samples return a false-negative result of “no virus detected, control succeeded” following any of several readily-encountered mishaps. This problem affects tens-of-millions of patients worth of shipped assays, but many of these flawed reagents have not yet been used. There is an opportunity to improve this important diagnostic tool. As demonstrated here, a re-designed transcript-specific control correctly monitors sample collection, extraction, reverse transcription, and qPCR detection. This approach can be rapidly implemented and will help reduce truly positive patients from being incorrectly given the all-clear. One Sentence Summary A widely-used COVID-19 diagnostic is mis-designed and generates false-negative results, dangerously confusing “No” with “Don’t know” – but it’s fixable


Covid-19, comment gérer un autre Titanic?


A novel presentation of COVID-19 via community acquired infection


docid: asyrijyg

title: Study on SARS-COV-2 transmission and the effects of control measures in China

text: Objective To reconstruct the transmission trajectory of SARS-COV-2 and analyze the effects of control measures in China. Methods Python 3.7.1 was used to write a SEIR class to model the epidemic procedure and a back propagation class to estimate the initial true infected number. The epidemic area in China was divided into three parts, Wuhan city, Hubei province (except Wuhan) and China (except Hubei) based on the different transmission pattern. A limitation factor for the medical resource was imposed to model the infected but not quarantined. Credible data source from Baidu Qianxi were used to assess the number of infected cases migrated from Wuhan to other areas. Results Basic reproduction number, R0, was 3.6 in the very early stage. The true infected number was 4508 in our model in Wuhan before January 22, 2020. By January 22 2020, it was estimated that 1764 infected cases migrated from Wuhan to other cities in Hubei province. Effective reproductive number, R, gradually decreased from 3.6 (Wuhan, stage 1), 3.4 (Hubei except Wuhan, stage 1) and 3.3 (China except Hubei, stage 1) to 0.67 (Wuhan, stage 4), 0.83 (Hubei except Wuhan, stage 2) and 0.63 (China except Hubei, stage 2), respectively. Especially after January 23, 2020 when Wuhan City was closed, the infected number showed a turning point in Wuhan. By early April, there would be 42073, 21342 and 13384 infected cases in Wuhan, Hubei (except Wuhan) and China (except Hubei) respectively, and there would be 2179, 633 and 107 death in Wuhan, Hubei (except Wuhan) and China (except Hubei) respectively. Conclusion A series of control measures in China have effectively prevented the spread of COVID-19, and the epidemic will end in early April.


title: The Endothelial Dysfunction and Pyroptosis Driving the SARS-CoV-2 Immune-Thrombosis

text: Objective: Endothelial activation after viral infection could contribute to changes in the vascular glycocalyx associated with programmed inflammatory cell death called pyroptosis. Thus, our goal is to recognize endothelial activation and pyroptosis in lung and myocardial samples of Coronavirus disease (COVID-19) cases and compare to H1N1pdm09 and control cases. Approach and Results: Post-mortem lung (6 cases of COVID-19 group; 10 cases of H1N1 group and 11 cases of Control group) and myocardial samples (2 cases of COVID-19 and one control) were analyzed by conventional immunohistochemistry by using antibodies to identify molecules involving with endothelial activation (CD163, Interleukin-6 (IL-6), Tumor Necrosis Factor alpha (TNF-alpha), Intercellular Adhesion Molecule 1 (ICAM-1)) and pyroptosis (Caspase-1). As a result, IL-6, TNF-alpha, ICAM-1, and Caspase-1 show higher tissue expression in the COVID-19 group compared to H1N1 and Control groups. Conclusion: Our results indicate that the vascular endothelium has been activated and the presence of pyroptosis and endothelial dysfunction in lung and myocardial samples. These conditions could lead to a systemic immune-thrombotic process that may impair the clinical staff's efforts to prevent fatal outcomes. One aim of the health professionals is to avoid COVID-19 systemic vascular injury and immune-thrombosis by blocking the endothelial dysfunction and its consequences.


title: Growth factor receptor signaling inhibition prevents SARS-CoV-2 replication

text: SARS-CoV-2 infections are rapidly spreading around the globe. The rapid development of therapies is of major importance. However, our lack of understanding of the molecular processes and host cell signaling events underlying SARS-CoV-2 infection hinder therapy development. We employed a SARS-CoV-2 infection system in permissible human cells to study signaling changes by phospho-proteomics. We identified viral protein phosphorylation and defined phosphorylation-driven host cell signaling changes upon infection. Growth factor receptor (GFR) signaling and downstream pathways were activated. Drug-protein network analyses revealed GFR signaling as key pathway targetable by approved drugs. Inhibition of GFR downstream signaling by five compounds prevented SARS-CoV-2 replication in cells, assessed by cytopathic effect, viral dsRNA production, and viral RNA release into the supernatant. This study describes host cell signaling events upon SARS-CoV-2 infection and reveals GFR signaling as central pathway essential for SARS-CoV-2 replication. It provides with novel strategies for COVID-19 treatment.


title: The scale and dynamics of COVID-19 epidemics across Europe

text: The frequently stated goal of COVID-19 control is to 'flatten the curve'; that is, to slow the epidemic by limiting contacts between infectious and susceptible individuals, and to reduce and delay peak numbers of cases and deaths. Here we investigate how the scale and dynamics of COVID-19 epidemics differ among 26 European countries in which the numbers of reported deaths varied more than 100-fold. Under lockdown, countries reporting fewer deaths in total also had lower peak death rates, as expected, but shorter rather than longer periods of epidemic growth. This empirical analysis highlights the benefits of intervening early to curtail COVID-19 epidemics: the cumulative number of deaths reported in each country by 20 June was 60-200 times the number reported by the date of lockdown.


title: Not wearing masks to protect against coronavirus is a ‘big mistake,’ top Chinese scientist says

text: Chinese scientists at the front of that country’s outbreak of coronavirus disease 2019 (COVID-19) have not been particularly accessible to foreign media Many have been overwhelmed trying to understand their epidemic and combat it, and responding to media requests, especially from journalists outside of China, has not been a top priority Science has tried to interview George Gao, director-general of the Chinese Center for Disease Control and Prevention (CDC), for 2 months Last week he responded


title: A scaling approach to estimate the COVID-19 infection fatality ratio from incomplete data

text: SARS-CoV-2 has disrupted the life of billions of people around the world since the first outbreak was officially declared in China at the beginning of 2020. Yet, important questions such as how deadly it is or its degree of spread within different countries remain unanswered. In this work, we exploit the 'universal' growth of the mortality rate with age observed in different countries since the beginning of their respective outbreaks, combined with the results of the antibody prevalence tests in the population of Spain, to unveil both unknowns. We validate these results with an analogous antibody rate survey in the canton of Geneva, Switzerland. We also argue that the official number of deaths over 70 years old is importantly underestimated in most of the countries, and we use the comparison between the official records with the number of deaths mentioning COVID-19 in the death certificates to quantify by how much. Using this information, we estimate the fatality infection ratio (IFR) for the different age segments and the fraction of the population infected in different countries assuming a uniform exposure to the virus in all age segments. We also give estimations for the non-uniform IFR using the sero-epidemiological results of Spain, showing a very similar growth of the fatality ratio with age. Only for Spain, we estimate the probability (if infected) of being identified as a case, being hospitalized or admitted in the intensive care units as function of age. In general, we observe a nearly exponential growth of the fatality ratio with age, which anticipates large differences in total IFR in countries with different demographic distributions, with numbers that range from 1.82% in Italy, to 0.62% in China or even 0.14% in middle Africa.


title: Antiviral Decoction of Isatidis Radix (板藍根 bǎn lán gēn) Inhibited Influenza Virus Adsorption on MDCK Cells by Cytoprotective Activity

text: Abstract The aim of this study is to elucidate how the Isatidis Radix (板藍根 bǎn lán gēn) tonic, as an aqueous mixture of hundreds of compositions, interrupts the infection of influenza viruses to their host cells. The efficacy of the tonic was evaluated and expressed as cell proliferation rate and plaque reduction rate in Madin-Darby Canine Kidney (MDCK) cells, against 3 strains of influenza A and B viruses. This boiling water (at 100°C) extract of Isatidis Radix (RIE) showed antiviral activity against influenza virus A and B. The concentration for 50% inhibition of influenza virus A replication (IC50) in MDCK cell was 12.6mg/mL with a therapeutic index >8. When cells were incubated with RIE prior to virus adsorption, the numbers of viable cell were at least doubled compared to the numbers of virus control, RIE incubation after virus adsorption and RIE incubation with virus prior to adsorption, in both influenza virus A and B. Moreover, much less virus particles were spotted by scanning electron microscope (SEM) in the RIE pre-treated cells than the cells without RIE treatment. These results indicate the antiviral activity of RIE is mainly attributed to its host cell protection effect but not actions on virus or post-virus-adsorption interruption. Cell, but not virus, is more likely to be the action target of RIE.


title: COVID-19 Impact Among Spine Surgeons in Latin America

text: Study Design: Cross-sectional study. Objective: The aim of this study was to evaluate the impact of the COVID-19 outbreak in spine surgeons in Latin America. Methods: A questionnaire was sent to Latin American spine surgeons from April 4 to 6, 2020. Surgeon characteristics were recorded. The impact of COVID-19 on economic well-being, work, and mental health were also determined. All variables were compared and analyzed. Results: Two hundred four surgeons answered the complete survey; most of them were male (96.6%), the average age was 47.7 years; 58.8% (n = 120) were orthopedic surgeons and 41.2% (n = 84) were neurosurgeons. The majority of the respondents were from Argentina (59.8%, n = 122), followed by Brazil (17.2%, n = 35), Chile (6.4%, n = 13), and Mexico (5.9%, n = 12). Most of the surgeons reported performing emergency procedures only during the pandemic (76.5%, n = 156). Half used telemedicine or online consultation modalities (54.4%, n = 111). The average concern about the financial situation due to the pandemic was 7.53 in a scale of 1 to 10 (10 being the worst scenario). Twenty-two percent (n = 45) of the surgeons had a score over 10 in the Patient Health Questionnaire (PHQ-9; scores higher than 10 needs referral to confirm depression diagnosis). Young age and neurosurgery as a specialty were associated with higher PHQ-9 scores. Conclusions: COVID-19 has an impact in the daily working practice and financial situation of spine surgeons in Latin America. The long-term psychological impact should be taken into consideration to avoid a heavier burden for health care providers.


title: Adverse effects of COVID-19 related lockdown on pain, physical activity and psychological wellbeing in people with chronic pain

text: Countries across the world imposed lockdown restrictions during the COVID-19 pandemic. It has been proposed that lockdown conditions disproportionately impact those living with chronic pain, requiring adaptation to treatment and care strategies. We investigated how lockdown restrictions in the United Kingdom impacted individuals with chronic pain (N=431) relative to a healthy control group (N=88) using an online survey. In accordance with the fear-avoidance model, we hypothesised increases in perceived pain and psychological distress that would be mediated by pain catastrophizing. Survey questions answered during the lockdown period, probing patients self-perceived changes retrospectively, revealed that people with chronic pain perceived increases in their pain severity compared to before lockdown. They were also more adversely affected by lockdown compared to pain-free individuals, demonstrating greater increases in anxiety and depressed mood, increased loneliness and reduced levels of physical exercise. Pain catastrophizing was found to be an important factor in predicting the extent of self-perceived increases in pain, and accounted for the relationship between decreased mood and pain. Perceived decreases in levels of physical exercise also independently predicted perceptions of increased pain. Interestingly, actual changes in pain symptoms (measured at two time points at pre- and post-lockdown in a subgroup, N = 85) did not change significantly on average, but those reporting increases also demonstrated greater baseline levels of pain catastrophizing. Overall, the findings suggest that remote pain management provision to target reduction of catastrophizing and increases to physical activity could be beneficial for chronic pain patients in overcoming the adverse effects of lockdown.


How control theory can help us control Covid-19


title: Quantifying and mitigating the impact of the COVID-19 pandemic on outcomes in colorectal cancer

text: Background: The COVID-19 pandemic has caused disruption across cancer pathways for diagnosis and treatment. In England, 32% of colorectal cancer (CRC) is diagnosed via urgent symptomatic referral from primary care, the "2-week-wait" (2WW) pathway. Access to routine endoscopy is likely to be a critical bottleneck causing delays in CRC management due to chronic limitation in capacity, acute competition for physician time, and safety concerns. Methods: We used age-specific, stage-specific 10 year CRC survival for England 2007-2017 and 2WW CRC cases volumes. We used per-day hazard ratios of CRC survival generated from observational studies of CRC diagnosis-to-treatment interval to model the effect of different durations of per-patient delay. We utilised data from a large London observational study of faecal immunochemical testing (FIT) in symptomatic patients to model FIT-triage to mitigate delay to colonoscopy. Findings: Modest delays result in significant reduction in survival from CRC with a 4-month delay resulting across age groups in [≥]20% reduction in survival in Stage 3 disease and in total over a year, 1,419 attributable deaths across the 11,266 CRC patients diagnosed via the 2WW pathway. FIT triage of >10 ug Hb/g would salvage 1,292/1,419 of the attributable deaths and reduce colonoscopy requirements by >80%. Diagnostic colonoscopy offers net survival in all age groups, providing nosocomial COVID-19 infection rates are kept low (<2.5%). Interpretation To avoid significant numbers of avoidable deaths from CRC, normal diagnostic and surgical throughput must be maintained. An accrued backlog of cases will present to primary care following release of lockdown, supranormal endoscopy capacity will be required to manage this without undue delays. FIT-triage of symptomatic cases provides a rational approach by which to avoid patient delay and mitigate pressure on capacity in endoscopy. This would also reduce exposure to nosocomial COVID-19 infection, relevant in particular to older patient groups. Funding: Breast Cancer Now, Cancer Research UK, Bobby Moore Fund for Cancer Research, National Institute for Health Research (NIHR).


title: COVID-19 Growth Rate Decreases with Social Capital

text: Background: Social capital has been associated with many public health variables including mortality, obesity, diabetes, and sexually-transmitted disease rates. However, the relationship of social capital to the spread of infectious disease like COVID-19 is lacking. The COVID-19 pandemic presents an unprecedented threat to global health and economy, for which control strategies have relied on aggressive social distancing. However, an understanding of how social capital is related to changes in human mobility patterns for adherence to social distancing is lacking. Objective: This study examines the association between state- and county-level social capital indices and community health indices in the United States, and the growth rate of COVID-19 cases. It also examines changes in human mobility. Methods: Using publicly available state- and county-specific time series data for COVID-19 cases from March 13 to March 31, we used exponential fits to determine growth rate. We obtained publicly available mobility change data, originally measured from GPS-enabled mobile devices. The design was then state- and county-level correlation analysis with social capital and community health indices from the Social Capital Project (United States Senate). Results: In bivariate linear correlation analyses, we find social capital and community health indices were negatively associated with COVID-19 growth rates at both the state and county levels. The correlation was strongest at the county level for the community health index: a one-unit increase in the county community health index was associated with a decrease in the COVID-19 growth rate exponent by 0.045. In further bivariate correlation analyses, we find that social capital indices were negatively associated with retail/recreation movement and positively associated with residential movement. That is, an increase in social capital is correlated with slower COVID-19 infection spread and more adherence to social distancing protocols. Conclusion: Our results indicate the potential benefit of incorporating social capital concepts in planning policies to control the spread of COVID-19, e.g. different social distancing requirements in different communities. The results also indicate a need for further research into this potentially causal relationship, including examining interventions to increase social capital, community health, and institutional health.


title: Predictive Modeling on the Number of Covid-19 Death Toll in the United States Considering the Effects of Coronavirus-Related Changes and Covid-19 Recovered Cases

text: COVID-19 is caused by a coronavirus called SARS-CoV-2. Many countries around the world implemented their own policies and restrictions designed to limit the spread of Covid-19 in recent months. Businesses and schools transitioned into working and learning remotely. In the United States, many states were under strict orders to stay home at least in the month of April. In recent weeks, there are some significant changes related restrictions include social-distancing, reopening states, and staying-at-home orders. The United States surpassed 2 million coronavirus cases on Monday, June 15, 2020 less than five months after the first case was confirmed in the country. The virus has killed at least 115,000 people in the United States as of Monday, June 15, 2020, according to data from Johns Hopkins University. With the recent easing of coronavirus-related restrictions and changes on business and social activity such as stay-at-home, social distancing since late May 2020 hoping to restore economic and business activities, new Covid-19 outbreaks are on the rise in many states across the country. Some researchers expressed concern that the process of easing restrictions and relaxing stay-at-home orders too soon could quickly surge the number of infected Covid-19 cases as well as the death toll in the United States. Some of these increases, however, could be due to more testing sites in the communities while others may be are the results of easing restrictions due to recent reopening and changed policies, though the number of daily death toll does not appear to be going down in recent days due to Covid-19 in the U.S. This raises the challenging question: * How can policy decision-makers and community leaders make the decision to implement public policies and restrictions and keep or lift staying-at-home orders of ongoing Covid-19 pandemic for their communities in a scientific way? In this study, we aim to develop models addressing the effects of recent Covid-19 related changes in the communities such as reopening states, practicing social-distancing, and staying-at-home orders. Our models account for the fact that changes to these policies which can lead to a surge of coronavius cases and deaths, especially in the United States. Specifically, in this paper we develop a novel generalized mathematical model and several explicit models considering the effects of recent reopening states, staying-at-home orders and social-distancing practice of different communities along with a set of selected indicators such as the total number of coronavirus recovered and new cases that can estimate the daily death toll and total number of deaths in the United States related to Covid-19 virus. We compare the modeling results among the developed models based on several existing criteria. The model also can be used to predict the number of death toll in Italy and the United Kingdom (UK). The results show very encouraging predictability for the proposed models in this study. The model predicts that 128,500 to 140,100 people in the United States will have died of Covid-19 by July 4, 2020. The model also predicts that between 137,900 and 154,000 people will have died of Covid-19 by July 31, and 148,500 to 169,700 will have died by the end of August 2020, as a result of the SARS-CoV-2 coronavirus that causes COVID-19 based on the Covid-19 death data available on June 13, 2020. The model also predicts that 34,900 to 37,200 people in Italy will have died of Covid-19 by July 4, and 36,900 to 40,400 people will have died by the end of August based on the data available on June 13, 2020. The model also predicts that between 43,500 and 46,700 people in the United Kingdom will have died of Covid-19 by July 4, and 48,700 to 51,900 people will have died by the end of August, as a result of the SARS-CoV-2 coronavirus that causes COVID-19 based on the data available on June 13, 2020. The model can serve as a framework to help policy makers a scientific approach in quantifying decision-makings related to Covid-19 affairs.


title: Acceptability of app-based contact tracing for COVID-19: Cross-country survey evidence

text: Background: The COVID-19 pandemic is the greatest public health crisis of the last 100 years. Countries have responded with various levels of lockdown to save lives and stop health systems from being overwhelmed. At the same time, lockdowns entail large socio-economic costs. One exit strategy under consideration is a mobile phone app that traces close contacts of those infected with COVID- 19. Recent research has demonstrated the theoretical effectiveness of this solution in different disease settings. However, concerns have been raised about such apps because of the potential privacy implications. This could limit the acceptability of app-based contact tracing among the general population. As the effectiveness of this approach increases strongly with app take-up, it is crucial to understand public support for this intervention. Objectives: The objective of this study is to investigate user acceptability of a contact-tracing app in five countries hit by the pandemic. Methods We conducted a multi-country, large-scale (N = 5995) study to measure public support for digital contact tracing of COVID-19 infections. We ran anonymous online surveys in France, Germany, Italy, the UK and the US. We measured intentions to use a contact-tracing app across different installation regimes (voluntary installation vs. automatic installation by mobile phone providers), and studied how these intentions vary across individuals and countries. Results: We found strong support for the app under both regimes, in all countries, across all sub-groups of the population, and irrespective of regional-level COVID-19 mortality rates. We inves- tigated the main factors that may hinder or facilitate take-up and found that concerns about cyber security and privacy, together with lack of trust in government, are the main barriers to adoption. Conclusions: Epidemiological evidence shows that app-based contact-tracing can suppress the spread of COVID-19 if a high enough proportion of the population uses the app and that it can still reduce the number of infections if take-up is moderate. Our findings show that the willingness to install the app is very high. The available evidence suggests that app-based contact tracing may be a viable approach to control the diffusion of COVID-19.


title: A Case of a COVID-19-positive Patient

text: The coronavirus (COVID-19), discovered in 2019, has been creating havoc since it first emerged in China and is now spreading worldwide. Its presentation is somewhat similar to influenza. We hereby discuss the salient features of the coronavirus and present the case of a 33-year-old male who was tested positive for COVID-19.


title: Experimental investigation on the effect of crystal orientation of diamond tooling on micro laser assisted diamond turning of zinc sulfide

text: Abstract The present article reports on an experimental study of the effect of crystallographic orientation of single crystal diamond on ductile material removal of ZnS. A multispectral ZnS workpiece was machined with single crystal diamond tools having two different configurations of cutting plane and cutting direction. An x-ray diffractometer (XRD) was used to evaluate the cutting plane and cutting direction of each tool. It was observed that the tools having a {100} cutting plane and <110> cutting direction resulted in considerably lower tool wear and surface roughness values, to that of tools with similar cutting plane orientation and <100> cutting direction.


title: Pandemic (COVID‐19) Policy, Regional Cooperation and the Emerging Global Production Network(†)

text: In this paper, we explore the possible policy responses to the COVID‐19 pandemic shock as well as the related economic (financial crisis) shocks on trade and global value chains (GVC) in East Asia. We find that regional policy coordination is critical to mitigate and isolate the pandemic shock. It is important to identify the pandemic events early to flatten the pandemic curve at the national and regional level. This supports a recent study by the World Bank (2020), which highlights the importance of early mitigation policies during the pandemic shock. The cost of the pandemic and economic shocks will increase significantly when several countries in the region experience the pandemic shock concurrently. In this case, flattening the regional pandemic curve becomes important. The results also indicate the need for greater coordination in East Asia to mitigate the pending economic shock in terms of unemployment, corporate bankruptcy and financial market fragility. The paper also highlights that the stability of the GVC network is critical during the pandemic in terms of hedging the risk of disruptions to the procurement of critical medical and health products as well as maintaining service linkages to manufacturing, such as the logistics sector. Regional policy coordination and the stability of GVC will be valuable in the post‐pandemic recovery of the region.


title: A Novel Multi-ventilation Technique to Split Ventilators

text: Background: Despite efforts to initially contain Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2), it has spread worldwide and has strained international healthcare systems to the point where advanced respiratory resources and ventilators are depleted. This study aims to explore splitting ventilators, or multi-ventilation, as a viable alternative in these demanding times. We investigated whether individualized tidal volume and positive end expiratory pressure (PEEP) delivery is possible to lungs of different compliances that are being simultaneously ventilated from one anesthesia ventilator. Methods: We performed a controlled experiment in an operating room environment without animal or human participants. Two test lungs were connected to distinct modified Y-pieces that were ventilated in parallel from a single anesthesia ventilator. Results: Ventilation can be manipulated to qualitatively deliver individually tailored tidal volumes in the setting of varying PEEP and compliance requirements in pressure control mode. Conclusions: Splitting ventilators, or multi-ventilation, is a viable alternative to acute ventilator shortage during a pandemic. Ventilators can be split for individualized tidal volume and positive end-expiratory pressure delivery in multiple subjects of differing compliances and demographics.


title: Reconciling early-outbreak estimates of the basic reproductive number and its uncertainty: framework and applications to the novel coronavirus (SARS-CoV-2) outbreak

text: A novel coronavirus (SARS-CoV-2) has recently emerged as a global threat. As the epidemic progresses, many disease modelers have focused on estimating the basic reproductive number Ro -- the average number of secondary cases caused by a primary case in an otherwise susceptible population. The modeling approaches and resulting estimates of Ro vary widely, despite relying on similar data sources. Here, we present a novel statistical framework for comparing and combining different estimates of Ro across a wide range of models by decomposing the basic reproductive number into three key quantities: the exponential growth rate $r$, the mean generation interval $\bar G$, and the generation-interval dispersion $\kappa$. We then apply our framework to early estimates of Ro for the SARS-CoV-2 outbreak. We show that many early Ro estimates are overly confident. Our results emphasize the importance of propagating uncertainties in all components of Ro, including the shape of the generation-interval distribution, in efforts to estimate Ro at the outset of an epidemic.


title: A data-driven model for predicting the course of COVID-19 epidemic with applications for China, Korea, Italy, Germany, Spain, UK and USA

text: For an emergent disease, such as Covid-19, with no past epidemiological data to guide models, modelers struggle to make predictions of the course of the epidemic (Cyranoski, Nature News 18 February 2020). The wildly varying predictions make it difficult to base policy decisions on. On the other hand much empirical information is already contained in data of evolving epidemiological profiles. We offer an additional tool, based on general theoretical principles and validated with data, for tracking the turning points, peak and accumulated case numbers of infected and recovered for an epidemic, and to predict its course. Ability to predict the turning points and the end of epidemic is of crucial importance for fighting the epidemic and planning for a return to normalcy. The accuracy of the prediction of the peaks of the epidemic is validated using data in different regions in China showing the effects of different levels of quarantine. The validated tool can be applied to other countries where Covid-19 has spread, and generally to future epidemics. US is found to have the largest net infection rate, and is predicted to have the largest total infected cases (708K) and will take two weeks longer than Wuhan to reach its turning point, and one week longer than Italy and Germany.


title: Antiviral Drug Screen of Kinase inhibitors Identifies Cellular Signaling Pathways Critical for SARS-CoV-2 Replication

text: Emergence of a highly contagious novel coronavirus, SARS-CoV-2 that causes COVID-19, has precipitated the current global health crisis with over 479,000 deaths and more than 9.3 million confirmed cases. Currently, our knowledge of the mechanisms of COVID-19 disease pathogenesis is very limited which has hampered attempts to develop targeted antiviral strategies. Therefore, we urgently need an effective therapy for this unmet medical need. Viruses hijack and dysregulate cellular machineries in order for them to replicate and infect more cells. Thus, identifying and targeting dysregulated signaling pathways that have been taken over by viruses is one strategy for developing an effective antiviral therapy. We have developed a high-throughput drug screening system to identify potential antiviral drugs targeting SARS-CoV-2. We utilized a small molecule library of 430 protein kinase inhibitors, which are in various stages of clinical trials. Most of the tested kinase antagonists are ATP competitive inhibitors, a class of nucleoside analogs, which have been shown to have potent antiviral activity. From the primary screen, we have identified 34 compounds capable of inhibiting viral cytopathic effect in epithelial cells. Network of drug and protein relations showed that these compounds specifically targeted a limited number of cellular kinases. More importantly, we have identified mTOR-PI3K-AKT, ABL-BCR/MAPK, and DNA-Damage Response (DDR) pathways as key cellular signaling pathways critical for SARS-CoV-2 infection. Subsequently, a secondary screen confirmed compounds such as Berzosertib (VE-822), Vistusertib (AZD2014), and Nilotinib with anti SARS-CoV-2 activity. Finally, we found that Berzosertib, an ATR kinase inhibitor in the DDR pathway, demonstrated potent antiviral activity in a human epithelial cell line and human induced pluripotent stem cell (hIPSC)-derived cardiomyocytes. These inhibitors are already in clinical trials of phase 2 or 3 for cancer treatment, and can be repurposed as promising drug candidates for a host-directed therapy of SARS-CoV-2 infection. In conclusion, we have identified small molecule inhibitors exhibiting anti SARS-CoV-2 activity by blocking key cellular kinases, which gives insight on important mechanism of host-pathogen interaction. These compounds can be further evaluated for the treatment of COVID-19 patients following additional in vivo safety and efficacy studies. Disclosures None declared.


title: Estimation of Transmission Potential and Severity of COVID-19 in Romania and Pakistan

text: During the outbreak of an epidemic, it is of immense interest to monitor the effects of containment measures and forecast of outbreak including epidemic peak. To confront the epidemic, a simple S I R model is used to simulate the number of affected patients of Coronavirus disease in Romania and Pakistan. The model captures the growth in case onsets and the estimated results are almost compatible with the actual reported cases. Through the calibration of parameters, forecast for the appearance of new cases in Romania and Pakistan is reported till the end of this year by analysing the current situation. The constant level of number of patients and time-to-reach this level is also reported through the simulations. The drastic condition is also discussed which may occur if all the preventive restraints are removed.


title: SARS-CoV-2 antibody seroprevalence in industry workers in Split-Dalmatia and Sibenik-Knin County, Croatia

text: BACKGROUND As a result of global spread, COVID-19 has also affected the Republic of Croatia in the last week of February. Although official data show that the number of newly infected is declining, it is still unknown what proportion of the population has been affected by the disease. AIM To examine seroprevalence of SARS-CoV-2 antibodies in industry workers population sample. METHODS From 23 to 28 April 2020, we conducted serological testing for antibodies (IgG and IgM) on 1494 factory employees living in the Split-Dalmatia and Sibenik-Knin County (Croatia). We analysed antibody seroprevalence on the level of the company, county, and separately for employees living at the factory premises with limited mobility during the lockdown measures. RESULTS In a total sample of tested company employees, we detected antibodies in 1.27% of participants (95% CI 0.77-1.98%). In Split facility 13/1316 (0.99%, 95% CI 0.53-1.68%) of participants were tested positive, of which 13/1079 (1.20%, 95% CI 0.64-2.05%) of those living outside the facility and 0/237 (0%, 95% CI 0-1.26%) of those living inside the facility. In Knin facility, 6/178 (3.37%, 95% CI 1.25-7.19%) participants were tested positive for antibodies. The difference between Split (no mobility restrictions) and Knin, was not statistically significant ({chi}2 = 3.47, P = 0.062). CONCLUSIONS The study showed relatively small SARS-CoV-2 antibody seroprevalence in the DIV Group population sample. When the study findings are interpreted on the county levels, they could indicate that most of the counties' population was not exposed to the virus.


title: Part III-1. Positive-Strand RNA Viruses

text: Unknown


title: The clinical and epidemiological features and hints of 82 confirmed COVID-19 pediatric cases aged 0-16 in Wuhan, China

text: Although COVID-19 pediatric patients just account for 1% of the overall cases, they are nonnegligible invisible infection sources. We quantitatively analyzed the clinical and epidemiological features of 82 confirmed cases aged 0-16 admitted to Wuhan Children's Hospital, which are expected to shed some lights onto the pediatric diagnosis and therapy.


title: Phylogenomics and phylodynamics of SARS-CoV-2 retrieved genomes from India

text: The ongoing SARS-CoV-2 pandemic is one of the biggest outbreaks after the Spanish flu of 1918. Understanding the epidemiology of viral outbreaks is the first step towards vaccine development programs. This is the first phylodynamics study attempted on of SARS-CoV-2 genomes from India to infer its current evolution in the context of an ongoing pandemic. Out of 286 retrieved SARS-CoV-2 whole genomes from India, 138 haplotypes were generated and analyzed. Median-joining network was built to investigate the relatedness of SARS-CoV-2 haplotypes in India. The BDSIR package of BEAST2 was used to calculate the reproduction number (R0) and the infectious rate of the virus. Past and current population trend was investigated using the stamp date method in coalescent Bayesian skyline plot, implemented in BEAST2 and by exponential growth prior in BEAST 1.10.4. Median-joining network reveals two distinct ancestral clusters A and B showing genetic affinities with Wuhan outbreak sample. The network also illustrates the autochthonous development of isolates in a few instances. High basic reproduction number of SARS-nCoV-2 in India points towards the phase of active community transmission. The Bayesian skyline plot revel exponential rise in the effective population size (Ne) of Indian isolates from the first week of January to the first week of April 2020. More genome sequencing and analyses of the virus will be required in coming days to monitor COVID19 after the upliftment of lock down in India.


title: Blood parameters measured on admission as predictors of outcome for COVID-19; a prospective UK cohort study

text: Abstract: Introduction: COVID-19 has an unpredictable clinical course so prognostic biomarkers would be invaluable when triaging patients on admission to hospital. Many biomarkers have been suggested using large observational datasets but sample timing is crucial to ensure prognostic relevance. The DISCOVER study prospectively recruited patients with COVID-19 admitted to a UK hospital and analysed a panel of putative prognostic biomarkers on the admission blood sample to identify markers of poor outcome. Methods: Consecutive patients admitted to hospital with proven or clinicoradiological suspected COVID-19 were recruited. Admission bloods were extracted from the clinical laboratory. A panel of biomarkers (IL-6, suPAR, KL-6, Troponin, Ferritin, LDH, BNP, Procalcitonin) were performed in addition to routinely performed markers (CRP, neutrophils, lymphocytes, neutrophil:lymphocyte ratio). Age, NEWS score and CURB-65 were included as comparators. All biomarkers were tested in logistic regression against a composite outcome of non-invasive ventilation, intensive care admission, or death, with Area Under the Curve (AUC) figures calculated. Results: 155 patients had 28-day outcomes at the time of analysis. CRP (AUC 0.51 ,CI:0.40-0.62), lymphocyte count (AUC 0.62 ,CI:0.51-0.72), and other routine markers did not predict the primary outcome. IL-6 (AUC: 0.78,0.65-0.89) and suPAR (AUC 0.77 ,CI: 0.66-0.85) showed some promise, but simple clinical features alone such as NEWS score (AUC: 0.74 ,0.64-0.83) or age (AUC: 0.70 ,0.61-0.78) performed nearly as well. Discussion: Admission blood biomarkers have only moderate predictive value for predicting COVID-19 outcomes, while simple clinical features such as age and NEWS score outperform many biomarkers. IL-6 and suPAR had the best performance, and further studies should validate these biomarkers in a prospective fashion.


title: Prognostic value of visual quantification of lesion severity at initial chest CT in confirmed Covid-19 infection: a retrospective analysis on 216 patients

text: Rationale and Objectives Studies suggest an association between chest CT findings assessed with semiquantitative CT score and gravity of Covid-19. The objective of this work is to analyze potential correlation between visual quantification of lesion severity at initial chest CT and clinical outcome in confirmed Covid-19 patients. Materials and Methods From March 5 th to March 21 st , 2020, all consecutive patients that underwent chest CT for clinical suspicion of Covid-19 at a single tertiary center were retrospectively evaluated for inclusion. Patients with lung parenchyma lesions compatible with Covid- 19 and positive RT-PCR were included. Global extensiveness of abnormal lung parenchyma was visually estimated and classified independently by 2 readers, following the European Society of Thoracic Imaging Guidelines. Death and/or mechanical ventilation within 30 days following the initial chest CT was chosen as the primary hard endpoint. Results 216 patients (124 men, 62 years-old, range 22 ; 94 yo) corresponding to 216 chest CT were included. Correlation between lesion severity and percentage of patients that met the primary endpoint was high, with a coefficient p; of 0.87 (p = 0.05). A greater than 25% involvement was significantly associated with a higher risk of mechanical ventilation or death at 30 days, with a Risk Ratio of 5.00 (95% CI [3.59- 6.99]). Conclusion This retrospective cohort confirms a correlation between visual evaluation of lesions severity at initial chest CT and the 30 days clinical outcome of Covid-19 patients and suggests using a threshold of greater than 25% involvement to identify patients at risk.


A pandemia de COVID-19 no Brasil: Crônica de uma crise sanitária anunciada


title: Comparative Pathogenesis Of COVID-19, MERS And SARS In A Non-Human Primate Model

text: A novel coronavirus, SARS-CoV-2, was recently identified in patients with an acute respiratory syndrome, COVID-19. To compare its pathogenesis with that of previously emerging coronaviruses, we inoculated cynomolgus macaques with SARS-CoV-2 or MERS-CoV and compared with historical SARS-CoV infections. In SARS-CoV-2-infected macaques, virus was excreted from nose and throat in absence of clinical signs, and detected in type I and II pneumocytes in foci of diffuse alveolar damage and mucous glands of the nasal cavity. In SARS-CoV-infection, lung lesions were typically more severe, while they were milder in MERS-CoV infection, where virus was detected mainly in type II pneumocytes. These data show that SARS-CoV-2 can cause a COVID-19-like disease, and suggest that the severity of SARS-CoV-2 infection is intermediate between that of SARS-CoV and MERS-CoV. One Sentence Summary SARS-CoV-2 infection in macaques results in COVID-19-like disease with prolonged virus excretion from nose and throat in absence of clinical signs.


title: Identifiability of infection model parameters early in an epidemic

text: It is known that the parameters in the deterministic and stochastic SEIR epidemic models are structurally identifiable. For example, from knowledge of the infected population time series I(t) during the entire epidemic, the parameters can be successfully estimated. In this article we observe that estimation will fail in practice if only infected case data during the early part of the epidemic (pre-peak) is available. This fact can be explained using a long-known phenomenon called dynamical compensation. We use this concept to derive an unidentifiability manifold in the parameter space of SEIR that consists of parameters indistinguishable to I(t) early in the epidemic. Thus, identifiability depends on the extent of the system trajectory that is available for observation. Although the existence of the unidentifiability manifold obstructs the ability to exactly determine the parameters, we suggest that it may be useful for uncertainty quantification purposes. A variant of SEIR recently proposed for COVID-19 modeling is also analyzed, and an analogous unidentifiability surface is derived.


COVID-19: A Matter Close to the Heart


title: Informing epidemic (research) responses in a timely fashion by knowledge management - a Zika virus use case

text: The response of pathophysiological research to emerging epidemics often occurs after the epidemic and, as a consequence, has little to no impact on improving patient outcomes or on developing high-quality evidence to inform clinical management strategies during the epidemic. Rapid and informed guidance of epidemic (research) responses to severe infectious disease outbreaks requires quick compilation and integration of existing pathophysiological knowledge. As a case study we chose the Zika virus (ZIKV) outbreak that started in 2015 to develop a proof-of-concept knowledge repository. To extract data from available sources and build a computationally tractable and comprehensive molecular interaction map we applied generic knowledge management software for literature mining, expert knowledge curation, data integration, reporting and visualisation. A multi-disciplinary team of experts, including clinicians, virologists, bioinformaticians and knowledge management specialists, followed a pre-defined workflow for rapid integration and evaluation of available evidence. While conventional approaches usually require months to comb through the existing literature, the initial ZIKV KnowledgeBase (ZIKA KB) was completed within a few weeks. Recently we updated the ZIKA KB with additional curated data from the large amount of literature published since 2016 and made it publicly available through a web interface together with a step-by-step guide to ensure reproducibility of the described use case (S4). In addition, a detailed online user manual is provided to enable the ZIKV research community to generate hypotheses, share knowledge, identify knowledge gaps, and interactively explore and interpret data (S5). A workflow for rapid response during outbreaks was generated, validated and refined and is also made available. The process described here can be used for timely structuring of pathophysiological knowledge for future threats. The resulting structured biological knowledge is a helpful tool for computational data analysis and generation of predictive models and opens new avenues for infectious disease research. Availability www.zikaknowledgebase.eu Funding European Commission’s Seventh Framework Research Programme project PREPARE (FP7-Health n°602525) and ZIKALLIANCE (MK, H2020; No 734548). Author summary During the recent ZIKV outbreak there was little information about the interactions between Zika virus and the host, however, the massive research response lead to a steep increase in the number of relevant publications within a very short period of time. At the time, there was no structured and comprehensive database available for integrated molecular and physiological data and knowledge about ZIKV infection. Researchers had to manually review the literature (amounting to over 5000 articles on ZIKV during our last update of the ZIKA KB in September 2018) to extract information about host–pathogen interaction and affected molecular, cellular and organ pathways. We explored the use of automated literature analysis and a defined cooperative effort between experts from various scientific, biomedical and information-technology domains to rapidly compile existing pathophysiological knowledge as a potential tool to support investigations during an emergency. This tool is contrasted with conventional approaches that would take months to comb through the massive amount of existing literature. In addition to providing background information for research, scientific publications can be processed to transform textual information into complex networks, which can be integrated with existing knowledge resources to suggest novel hypotheses that potentially contribute to innovative infectious disease research approaches. This study shows that the knowledge extraction and mapping process required to inform clinical and research responses to an emerging epidemic can be efficiently and effectively executed with a dedicated and trained group of experts, a validated process and the necessary tools. Our results further provide an overview of ZIKV biology, allow prediction of drug efficacy and indentify specific host factors and signalling pathways affected by ZIKV.


Pandemia por nuevo Coronavirus: El amor en tiempos del Covid19/ Pandemic due to new Coronavirus: Love in times of Covid19


title: Diagnostic technology for COVID-19: comparative evaluation of antigen and serology-based SARS-CoV-2 immunoassays, and contact tracing solutions for potential use as at-home products

text: As the United States prepares to return to work and open up the economy in the midst of the COVID-19 pandemic without an available vaccine or effective therapy, testing and contact tracing are essential to contain and limit the spread of the COVID-19 virus. In response to the urgent public health need for accurate, effective, low-cost, and scalable COVID-19 testing technology, we evaluated and identified diagnostic solutions with potential for use as an at-home product. We conducted a deep horizon scan for antigen and serology-based diagnostics and down-selected to the most promising technologies. A total of 303 candidate products (138 antibody and 44 antigen tests) were identified. Product evaluations were based entirely on company-provided data. 73 serology-based antibody tests passing an initial scoring algorithm based on specificity and sensitivity data were then further evaluated using a second scoring algorithm. This second algorithm included a review of additional technical specifications of the devices, an analysis of supply chain, manufacturing, and distribution capacity of each vendor. 24 potential antibody products met the selection criteria for further direct laboratory evaluation. The performance metrics for selection of these 24 products are currently being evaluated in a Mass General Brigham laboratory. Testing alone might not be sufficient to prevent the spread of a highly contagious disease like COVID-19. Manual contact tracing could complement testing, but it is likely to fail in identifying many individuals who were in contact with a given COVID patient. The proliferation of smartphones in the population has enabled the development of solutions that can provide public health officials with valuable information for rapid and accurate contact tracing. Besides, electronic-based contact tracing solutions can be augmented by symptom self-reports gathered using electronic patient reported outcome (ePRO) platforms and by physiological data collected using wearable sensors. We performed a detailed assessment of 12 ePRO solutions, 27 wearable sensors, and 44 electronic-based contact tracing solutions. These technologies were evaluated using criteria developed to assess their suitability to address the COVID-19 pandemic. We identified a number of solutions that could augment if not provide a more effective alternative to manual contact tracing. Finally, we propose a theoretical framework in which ePRO platforms, wearable sensors, and electronic-based contact tracing solutions would be utilized in combination with molecular and serological tests to identify and isolate COVID-19 cases rapidly.


title: Use of a Single Ventilator to Support Multiple Patients: Modeling Tidal Volume Response to Heterogeneous Lung Mechanics

text: The COVID-19 pandemic is creating ventilator shortages in many countries that is sparking a conversation about placing multiple people on a single ventilator. However, on March 26th the American College of Chest Physicians (CHEST), along with other leading medical organizations, released a joint statement warning clinicians that attempting this technique could lead to poor outcomes and high mortality. Nevertheless, several hospitals around the United States and abroad are turning to this technique out of desperation (e.g. New York), but little data exists to guide their approach. The overall objective of this study is to utilize a computational model of mechanically ventilated lungs to assess how patient-specific lung mechanics and ventilator settings impact lung tidal volume (Vt). Methods: We developed a single compartment computational model of four patients connected to a shared ventilator and validated it against a similar experimental study. We used this model to evaluate how patient-specific lung compliance (C) and resistance (R) would impact Vt under 5 ventilator settings of pre-set PIP, PEEP, and I:E ratio (suggested by Farkas, J.D. MD as an approach by hospitals to manage multiple patients on a single ventilator). Results: Our computational model predicts Vt within 10% of experimental measurements. Using this model to perform a parametric study, we provide proof-of-concept for an algorithm to better match patients in different hypothetical scenarios of a single ventilator shared by more than one patient. Conclusions: Assigning patients to pre-set ventilators based on their lung mechanics could be used to overcome some of the legitimate concerns of placing multiple patients on a single ventilator. We emphasize that our results are currently based on a computational model that has not been validated against any pre-clinical/clinical data. Therefore, clinicians considering this approach should not look to our study as an exact estimate of predicted patient tidal volumes.


title: Analysis of COVID-19 spread in South Korea using the SIR model with time-dependent parameters and deep learning

text: Mathematical modeling is a process aimed at finding a mathematical description of a system and translating it into a relational expression. When a system is continuously changing over time (e.g., infectious diseases)differential equations, which may include parameters, are used for modeling the system. The process of finding those parameters that best fit the given data from the system is called an inverse problem. This study aims at analyzing the novel coronavirus infection (COVID-19) spread in South Korea using the susceptible-infected-recovered (SIR) model. We collect the data from Korea Centers for Disease Control & Prevention (KCDC). We assume that each parameter in the SIR model is a function of time so that we can compute important parameters, such as the basic reproduction number (R0), more delicately. Using neural networks, we propose a method to find the best time-varying parameters and the solution for the model simultaneously. Moreover, using time-dependent parameters, we find that traditional numerical algorithms, such as the Runge-Kutta methods, can successfully approximate the SIR model while fitting the COVID-19 data, thus modeling the propagation patterns of COVID-19 more precisely.


title: Gastrointestinal, and hepatic involvement in Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infection: A review

text: Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) infection has caused a pandemic Coronavirus Disease-19 (COVID-19) that began in Wuhan city, China, in December 2019. Till 14(th) April 19,39,801 people have been affected by this virus 1,20,897 of whom died. Though respiratory symptoms are the typical manifestation of this disease, gastrointestinal (GI) symptoms such as anorexia, nausea, vomiting, loss of taste sensation, diarrhea, abdominal pain, and discomfort have been reported. The pooled prevalence of GI symptom is 17.6% (95% confidence interval [CI], 12.3%–24.5%), as indicated in a meta-analysis. A few studies suggested that the presence of GI symptoms is associated with poorer prognosis. The virus is excreted in feces during the acute disease, and even after the nasopharyngeal swab has become negative for viral ribonucleic acid (RNA). Fecal viral excretion may have clinical significance due to possible feco-oral transmission of the infection. 10.5% to 53% of patients with COVID-19, particularly those with severe disease, have been shown to have an elevation of hepatic enzymes through biochemical and clinical jaundice, are uncommon. Knowledge about this disease in general and GI involvement, in particular, is currently evolving.


title: Snapshot PCR Surveillance for SARS-CoV-2 in Hospital Staff in England

text: Background Significant nosocomial transmission of SARS-CoV-2 has been demonstrated. Understanding the prevalence of SARS-CoV-2 carriage amongst HCWs at work is necessary to inform the development of HCW screening programmes to control nosocomial spread. Methods Cross-sectional snapshot survey from April-May 2020; HCWs recruited from six UK hospitals. Participants self-completed a health questionnaire and underwent a combined viral nose and throat swab, tested by Polymerase Chain Reaction (PCR) for SARS-CoV-2 with viral culture on majority of positive samples. Findings Point prevalence of SARS-CoV-2 carriage across the sites was 2.0% (23/1152 participants), median cycle threshold value 35.70 (IQR:32.42-37.57). 17 were previously symptomatic, two currently symptomatic (isolated anosmia and sore throat); the remainder declared no prior or current symptoms. Symptoms in the past month were associated with threefold increased odds of testing positive (aOR 3.46, 95%CI 1.38-8.67; p=0.008). SARS-CoV-2 virus was isolated from only one (5%) of nineteen cultured samples. A large proportion (39%) of participants reported symptoms in the past month. Interpretation The point-prevalence is similar to previous estimates for HCWs in April 2020, though a magnitude higher than in the general population. Based upon interpretation of symptom history and testing results including viral culture, the majority of those testing positive were unlikely to be infectious at time of sampling. Development of screening programmes must balance the potential to identify additional cases based upon likely prevalence, expanding the symptoms list to encourage HCW testing, with resource implications and risks of excluding those unlikely to be infectious with positive tests.


title: Air recirculation role in the infection with COVID-19, lessons learned from Diamond Princess cruise ship

text: Objectives: The Diamond Princess cruise ship is a unique case because it is the place at which testing capacity has reached its highest rate in the world during the COVID-19 pandemic. By analysing data that are collected about the current COVID-19 outbreak onboard, and by considering the design of the air conditioning system of the ship and virus transmission modes on cruise ships, this study aims to raise the hypothesis regarding the role of poor ventilation systems in the spread of COVID-19. Design: This is an analysis of count data that has been collected by the onboard clinic up to the 20th February 2020. Symptomatic infection rates during the quarantine period in cabins with previous confirmed cases are compared to these in cabins without previous confirmed cases. Results: Symptomatic infection rate during the quarantine period in cabins with previously confirmed cases is not significantly higher than that in cabins without previously confirmed cases. Age does not appear to be a cofounder. Conclusions: Airborne transmission of COVID-19 through the ventilation system onboard could explain the virus spread into cabins during the quarantine period.


title: Development and potential usefulness of the COVID-19 Ag Respi-Strip diagnostic assay in a pandemic context.

text: Introduction: COVID-19 Ag Respi-Strip, an immunochromatographic (ICT) assay for the rapid detection of SARS-CoV-2 antigen on nasopharyngeal specimen, has been developed to identify positive COVID-19 patients allowing prompt clinical and quarantine decisions. In this Original Research article, we describe the conception, the analytical and clinical performances as well as the risk management of implementing the COVID-19 Ag Respi-Strip in a diagnostic decision algorithm. Materials and Methods: Development of the COVID-19 Ag Respi-Strip resulted in a ready-to-use ICT assay based on a membrane technology with colloidal gold nanoparticles using monoclonal antibodies directed against the SARS-CoV and SARS-CoV-2 highly conserved nucleoprotein antigen. Four hundred observations were recorded for the analytical performance study and thirty tests were analysed for the cross-reactivity study. The clinical performance study was performed in a retrospective multi-centric evaluation on aliquots of 328 nasopharyngeal samples. COVID-19 Ag Respi-Strip results were compared with qRT-PCR as golden standard for COVID-19 diagnostics. Results: In the analytical performance study, the reproducibility showed a between-observer disagreement of 1.7%, a robustness of 98%, an overall satisfying user friendliness and no cross-reactivity with other virus-infected nasopharyngeal samples. In the clinical performance study performed in three different clinical laboratories we found an overall sensitivity and specificity of 57.6% and 99.5% respectively with an accuracy of 82.6%. The cut-off of the assay was found at Ct<22. User-friendliness analysis and risk management assessment through Ishikawa diagram demonstrate that COVID-19 Ag Respi-Strip may be implemented in clinical laboratories according to biosafety recommendations. Conclusion: The COVID-19 Ag Respi-Strip represents a promising rapid SARS-CoV-2 antigen assay for the first-line diagnosis of COVID-19 in 15 minutes. Its role in the proposed diagnostic algorithm is complementary to the currently-used molecular techniques.


title: Health-care preparedness and health-care worker protection in COVID-19 pandemic

text: The COVID-19 pandemic has ravaged the nations and has created the institution of unprecedented measures globally toward its containment. Extraordinary measures may be needed for health-care preparedness, to reduce morbidity and mortality. Health-care workers who are at the frontlines in such pandemics are the most vulnerable. These issues are addressed in this article.


docid: jbnvjnls

title: Impact of Governmental interventions on epidemic progression and workplace activity during the COVID-19 outbreak

text: In the first quarter of 2020, the COVID-19 pandemic brought the world to a state of paralysis. During this period, humanity has seen by far the largest organized travel restrictions and unprecedented efforts and global coordination to contain the spread of the SARS-CoV-2 virus. Using large scale human mobility and fine grained epidemic incidence data, we develop a framework to understand and quantify the effectiveness of the interventions implemented by various countries to control epidemic growth. Our analysis reveals the importance of timing and implementation of strategic policy in controlling the epidemic. Through our analysis, we also unearth significant spatial diffusion of the epidemic before and during the lock-down measures in several countries, casting doubt on the effectiveness or on the implementation quality of the proposed Governmental policies.


title: Ultra-sensitive nanozyme-based chemiluminescence paper test for rapid diagnosis of SARS-CoV-2 infection

text: The recently emerged coronavirus disease COVID-19 has now evolved into a global pandemic. Early detection is crucial for its effective control. Nucleic acid testing for viral pathogen and serological testing for host antibodies are playing important roles in current COVID-19 diagnosis. However, while nucleic acid testing is complicated, facility-restricted and time-consuming, antibody testing may result in high rates of false-negative diagnoses, especially during the early stages of viral infection. Thus, a more rapid and reliable test for both early COVID-19 diagnosis and whole-population screening is urgently needed. Here, we developed a novel nanozyme-based chemiluminescence paper assay for rapid and high-sensitive testing of SARS-CoV-2 spike antigen. Our paper test uses a newly established peroxidase-mimic Co-Fe@hemin nanozyme instead of natural HRP that catalytically amplifies the chemiluminescent signal, allowing for target concentrations to be as low as 0.1 ng/ml. Furthermore, our nanozyme-based chemiluminescence test exhibits a linear range that is 32-fold wider compared to ELISA tests. Importantly, testing is completed in less than 16 min, compared to 1-2 h required for ELISA or nucleic acid tests. Critically, signal detection is feasible using a smartphone camera. Ingredients for our test are simple and readily available, rendering overall cost considerably lower than those used in current diagnoses. In conclusion, our novel test provides a high-sensitive, point-of-care testing (POCT) approach for SARS-CoV-2 antigen detection, which should greatly increase current early screening capacities for suspected infections, and considerably lower demand for national healthcare resources.


title: Comorbidity and Sociodemographic determinants in COVID-19 Mortality in an US Urban Healthcare System

text: Background: New York City is the US epicenter of the coronavirus disease 2019 (COVID-19) pandemic. Early international data indicated that comorbidity contributes significantly to poor prognosis and fatality in patients infected with SARS-CoV-2. It is not known to what degree medical comorbidity and sociodemographic determinants impact COVID-19 mortality in the US. Methods: Evaluation of de-identified electronic health records of 7,592 COVID-19 patients confirmed by SARS-CoV-2 lab tests in New York City. Medical comorbidites and outcome of mortality, and other covariates, including clinical, sociodemographic, and medication measures were assessed by bivariate and multivariate logistic regression models. Results: Of common comorbid conditions (hypertension, chronic kidney disease, chronic obstructive pulmonary disease, asthma, obesity, diabetes, HIV, cancer), when adjusted for covariates, chronic kidney disease remained significantly associated with increased odds of mortality. Patients who had more than one comorbidities, former smokers, treated with Azithromycin without Hydroxychloroquine, reside within the boroughs of Brooklyn and Queens Higher had higher odds of death. Conclusions: Increasing numbers of comorbid factors increase COVID-19 mortality, but several clinical and sociodemographic factors can mitigate risk. Continued evaluation of COVID-19 in large diverse populations is important to characterize individuals at risk and improve clinical outcomes.


title: Novel coronavirus infection: Covid-19/ Yeni Koronavirüs İnfeksiyonu: COVID-19

text: Coronaviruses (CoV) are enveloped, single-chain positive RNA viruses constituting a fairly large family. 229E, OC43, NL63 and HKU1 species are common in humans, often causing mild to moderate respiratory infections. On the other hand, new coronaviruses have emerged, causing severe respiratory infection such as “severe acute respiratory syndrome” (SARS) in 2002 and “Middle East respiratory syndrome” (MERS) in 2012. The most recent coronavirus, SARS-CoV-2, causing COVID-19 disease was identified in 2019. While people of all ages are susceptible to COVID-19 infection, those with underlying chronic diseases and elderly age have increased susceptibility. There is no specific antiviral drug for COVID-19 infection. Therefore, treatment strategy is mostly aimed at supportive treatment and prevention of complications. The main protection measure is to avoid contact with the person infected with COVID-19. Following the identification of COVID-19 disease, it exceeded the region where it was located, the number of cases increased gradually, and intercontinental reports were made. COVID-19 is a highly pathogenic respiratory virus threatening global public health today. In order to eradicate the virus, it is necessary to clarify the source of the virus, to develop specific, effective treatments and a safe vaccine. Effective surveillance and appropriate infection control measures are critical to prevent the spread of the virus.


title: Minimizing the risk of international spread of coronavirus disease 2019 (COVID-19) outbreak by targeting travelers

text: The Coronavirus Disease-2019 (COVID-19) outbreak has become a global health emergency owing to its magnitude, attributed deaths, and its propensity to spread across the world. In-fact, owing to its quick spread across international boundaries and the resulting caseload, the disease has been declared as a Public Health Emergency of International Concern on 30 January 2020. It is worth noting that out of the 395 cases detected in other nations, 165 (41.8%) have a positive history of travel to China. As of now, the World Health Organization has not recommended for any restrictions on the travel or trade aspects, but has clearly specified that implementation of International Health Regulations should be strictly done at the airports and seaports. In conclusion, the COVID- 19 outbreak has created an alarm across the globe as the causative virus is novel in nature. However, strengthening of standard infection control practices and adoption of preventive measures for travelers can significantly minimize the threat of further transmission of the disease.


title: Cancer and risk of COVID-19 through a general community survey

text: Background: Data are limited on the risk of coronavirus disease 2019 (COVID-19) among individuals with cancer and whether cancer-related therapy exacerbates this risk. Methods: We evaluated the risk for coronavirus disease 2019 (COVID-19) among patients living with cancer compared to the general community and whether cancer-related treatments influence this risk. Data were collected from the COVID Symptom Study smartphone application since March 24, 2020 (United Kingdom), March 29 (U.S.), and April 29, 2020 (Sweden) through May 8, 2020. We used multivariate-adjusted odds ratios (aORs) of a positive COVID-19 test as well as predicted COVID-19 infection using a validated symptom model. Results: Among 23,266 participants with cancer and 1,784,293 without cancer, we documented 10,404 reports of a positive COVID-19 test. Compared to participants without cancer, those living with cancer had 62% increased risk of a positive COVID-19 test (95% CI: 1.37-1.91). Among patients with cancer, current treatment with chemotherapy/immunotherapy was associated with a nearly 2.5-fold increased risk of a positive test (aOR: 2.42; 95% CI: 1.81-3.25). The association between cancer and COVID-19+ was stronger among participants >65 years (aOR: 1.93; 95%CI: 1.51-2.46) compared to younger participants (aOR: 1.32; 95%CI: 1.06-1.64; Pinteraction<0.001); and among males (aOR: 1.71; 95%CI: 1.36-2.15) compared to females (aOR: 1.43; 95%CI: 1.14-1.79; Pinteraction=0.02). Conclusions: Individuals with cancer had a significantly increased risk of infection compared to the general community. Those treated with chemotherapy or immunotherapy were particularly at-risk of infection. Trial Registration: ClinicalTrials.gov NCT04331509


title: Modelling the transmission dynamics of COVID-19 in six high burden countries

text: The new coronavirus disease, officially known as COVID-19, originated in China in 2019 and has since spread around the globe. We presented a modified Susceptible-Latent-Infected-Removed (SLIR) compartmental model of COVID-19 disease transmission with nonlinear incidence during the epidemic period. We provided the model calibration to estimate parameters with day wise corona virus (COVID-19) data i.e. reported cases by worldometer from the period of 15th February to 30th March, 2020 in six high burden countries including Australia, Italy, Spain, USA, UK and Canada. We estimate transmission rates for each countries and found that the highest transmission rate country in Spain, which may be increase the new cases and deaths in Spain than the other countries. Sensitivity analysis was used to identify the most important parameters through the partial rank correlation coefficient method. We found that the transmission rate of COVID-19 had the largest influence on the prevalence. We also provides the prediction of new cases in COVID-19 until May 18, 2020 using the developed model and recommends, control strategies of COVID-19. The information that we generated from this study would be useful to the decision makers of various organizations across the world including the Ministry of Health in Australia, Italy, Spain, USA, UK and Canada to control COVID-19.


title: Risk assessment of novel coronavirus COVID-19 outbreaks outside China

text: We developed a computational tool to assess the risk of novel coronavirus outbreaks outside China. We estimate the dependence of the risk of a major outbreak in a country from imported cases on key parameters such as: (i) the evolution of the cumulative number of cases in mainland China outside the closed areas; (ii) the connectivity of the destination country with China, including baseline travel frequencies, the effect of travel restrictions, and the efficacy of entry screening at destination; (iii) the efficacy of control measures in the destination country (expressed by the local reproduction number Rloc). We found that in countries with low connectivity to China but with relatively high Rloc, the most beneficial control measure to reduce the risk of outbreaks is a further reduction in their importation number either by entry screening or travel restrictions. Countries with high connectivity but low Rloc benefit the most from policies that further reduce Rloc. Countries in the middle should consider a combination of such policies. Risk assessments were illustrated for selected groups of countries from America, Asia and Europe, and we investigated how their risks depend on those parameters, and how the risk is increasing in time as the number of cases in China is growing.


Editorial-embracing how scholarly publishing can build a new research culture, post - Covid-19


title: A Real-Time Statistical Model for Tracking and Forecasting COVID-19 Deaths, Prevalence and Incidence

text: Background: Pandemics do not occur frequently and when they do there is a paucity of predictive tools that could help drive government responses to mitigate worst outcomes. Here we provide a forecasting model that is based on measurable variables and that strives for simplicity over complexity to obtain stable convergent forecasts of death, prevalence, incidence, and safe days for social easing. Methods: We assume, based on prior pandemic data, that death rate rise and fall approximately follows a Gaussian distribution, which can be asymmetric, which we describe. By taking daily death data for foreign countries and U.S. states and fitting it to an appropriate Gaussian function provides an estimate of where in the cycle a particular population lies. From that time point one can integrate remaining time to obtain a final total death. By also using measured values for the time from infection to recovery or death and a mortality factor, the prevalence (active cases) and incidence (new cases) totals and rate curves can be constructed. It is also possible by setting a downward threshold on prevalence that an estimate of a minimum date to begin relaxing social restrictions may be considered. Results: To demonstrate the model we chose the most severe hot-bed countries and U.S. states as a test-bed to evolve and improve our model and to compare with other models. The model can readily be applied to other countries by inputting data from public data bases. We also compare our forecasts to the University of Washington (UW) IHME model and are reassuringly similar yet show less variability on a weekly basis. The sum of squares for error (SSE) for international and U.S. states, respectively, that we track are: 34% and 33% for our model vs. 49% and 59% for the IHME model. Conclusions: Our model appears closest to the UW IHME model; however, there are important differences and while both models forecast many of the same results of interest, each one offers unique benefits that the other does not. We believe that the model reported here excels for its simplicity, which makes the model easy to use.


title: Unrevealing sequence and structural features of novel coronavirus using in silico approaches: The main protease as molecular target

text: Direct-acting antivirals are effective tools to control viral infections. SARS-CoV-2 is a coronavirus associated with the epidemiological outbreak in late 2019. Previous reports showed that HIV-1 protease inhibitors could block SARS-CoV main protease. Based on that and using an in silico approach, we evaluated SARS-CoV-2 main protease as a target for HIV-1 protease inhibitors to reveal the structural features related to their antiviral effect. Our results showed that several HIV inhibitors such as lopinavir, ritonavir, and saquinavir produce strong interaction with the active site of SARS-CoV-2 main protease. Furthermore, broad library protease inhibitors obtained from PubChem and ZINC (www.zinc.docking.org) were evaluated. Our analysis revealed 20 compounds that could be clustered into three groups based on their chemical features. Then, these structures could serve as leading compounds to develop a series of derivatives optimizing their activity against SARS-CoV-2 and other coronaviruses. Altogether, the results presented in this work contribute to gain a deep understanding of the molecular pharmacology of SARS-CoV-2 treatment and validate the use of protease inhibitors against SARS-CoV-2.


title: Estimation of Case Fatality Rate during an Epidemic: an Example from COVID-19 Pandemic

text: The case fatality rate (CFR) is an important index in epidemics and policymakers need to be aware of this statistic for making sound decisions. However, there are some uncertainties in the calculation of the fatality rate and the true case fatality rate can be calculated after an epidemic subsides, we calculated the fatality rate for 20 countries which had the highest number of confirmed cases with three scenarios. In this study, we provided detailed information to discuss the studies that calculate the case fatality rate during the COVID-19 pandemic and highlight the estimation bias in these studies


title: Coronavirus concerns force Arctic mission to cancel research flights

text: The global coronavirus outbreak is now curtailing research at the top of the world Travel restrictions imposed by Norway have forced the cancellation of research flights in support of the Polarstern, the icebound German research ship that is the centerpiece of a $150 million mission to study the effects of climate change on the Arctic


title: Deep Learning for Screening COVID-19 using Chest X-Ray Images

text: With the ever increasing demand for screening millions of prospective "novel coronavirus" or COVID-19 cases, and due to the emergence of high false negatives in the commonly used PCR tests, the necessity for probing an alternative simple screening mechanism of COVID-19 using radiological images (like chest X-Rays) assumes importance. In this scenario, machine learning (ML) and deep learning (DL) offer fast, automated, effective strategies to detect abnormalities and extract key features of the altered lung parenchyma, which may be related to specific signatures of the COVID-19 virus. However, the available COVID-19 datasets are inadequate to train deep neural networks. Therefore, we propose a new concept called domain extension transfer learning (DETL). We employ DETL, with pre-trained deep convolutional neural network, on a related large chest X-Ray dataset that is tuned for classifying between four classes viz, normal, other_disease, pneumonia and Covid-19. A 5-fold cross validation is performed to estimate the feasibility of using chest X-Rays to diagnose COVID-19. The initial results show promise, with the possibility of replication on bigger and more diverse data sets. The overall accuracy was measured as 95.3%{+/-}0.02. In order to get an idea about the COVID-19 detection transparency, we employed the concept of Gradient Class Activation Map (Grad-CAM) for detecting the regions where the model paid more attention during the classification. This was found to strongly correlate with clinical findings, as validated by experts.


Covid-19: Invisible, Elusive and the Advancing Enemy


title: Acid exposure impairs mucus secretion and disrupts mucus transport in neonatal piglet airways

text: Tenacious mucus produced by tracheal and bronchial submucosal glands is a defining feature of cystic fibrosis (CF). Although airway acidification occurs early in CF, whether transient acidification is sufficient to initiate mucus abnormalities is unknown. We studied mucus secretion and mucus transport in piglets forty-eight hours following an intra-airway acid challenge. Acid-challenged piglet airways were distinguished by increased mucin 5B (MUC5B) in the submucosal gland but decreased lung lavage fluid MUC5B, following in vivo cholinergic stimulation, suggesting a failure in submucosal gland secretion. Concomitantly, intrapulmonary airways were obstructed with glycoprotein rich material under both basal and methacholine-stimulated conditions. To mimic a CF-like environment, we also studied mucus secretion and transport under diminished bicarbonate and chloride transport conditions ex vivo. Cholinergic stimulation in acid-challenged piglet airways induced extensive mucus films, greater mucus strand formation, increased dilation of submucosal gland duct openings and decreased mucociliary transport. Finally, to elucidate potential mediators of acid-induced mucus defects, we investigated diminazene aceturate, a small molecule that inhibits the acid-sensing ion channel (ASIC). Diminazene aceturate restored surface MUC5B in acid-challenged piglet airways under basal conditions, mitigated acid-induced airway obstruction, and magnified the number of dilated submucosal gland duct openings. These findings suggest that even transient airway acidification early in life might have profound impacts on mucus secretion and transport properties. Further they highlight diminazene aceturate as an agent that might be beneficial in alleviating certain mucus defects in CF airway disease. One sentence summary Early life airway acidification has profound impacts on mucus secretion and transport.


docid: nnlynjoy

title: Effect of continuous renal replacement therapy on all-cause mortality in COVID-19 patients undergoing invasive mechanical ventilation: a retrospective cohort study

text: Background: Since December 2019, when coronavirus disease 2019 (COVID 19) emerged in Wuhan and rapidly spread throughout the world, critically ill patients have a high mortality rate. We aimed to assess the effect of continuous renal replacement therapy (CRRT) on all cause mortality in patients with COVID 19 undergoing invasive mechanical ventilation. Methods: In this retrospective cohort study, we included all patients with COVID 19 undergoing invasive mechanical ventilation at Optical Valley Branch of Tongji Hospital Affiliated with Tongji Medical College, Huazhong University of Science and Technology, Wuhan from February 12th to March 2nd, 2020. Demographic, clinical, laboratory, and treatment data were collected and analyzed. All patients were followed until death or end of follow up (March 9th), and all survivors were followed for at least one week. Findings: Of 36 hospitalized COVID-19 patients with invasive mechanical ventilation, the mean age was 69.4 (SD 1.8) years and 30 (83.3%) were men. 22 (61.1%) patients received CRRT (CRRT group) and 14 cases (38.9%) were managed in conventional strategy (non CRRT group). There was no difference in age, sex, comorbidities, complications, treatments and most of the laboratory findings, except for patients in the CRRT group with higher levels of aspartate aminotransferase and serum creatinine. During the average follow-up period of 10.4 days, 12 of 22 (54.5%) patients in CRRT group and 11 of 14 (78.6%) patients in non CRRT group died. Kaplan Meier analysis demonstrated a prolonged survival in patients in CRRT group than non CRRT group (P=0.032). The association between CRRT treatment and a reduced risk of mortality remained significant after adjusting for confounding factors in seven different models, with an adjusted hazard ratio (aHR) varying between 0.283 and 0.424. Older age, higher levels of IL1b, IL2 receptor, hs cTnI and NT proBNP were independently associated with increased risk of mortality in patients with CRRT treatment. Interpretation: CRRT may be beneficial for the treatment of COVID 19 patients with invasive mechanical ventilation. Further prospective multicenter studies with larger sample sizes are required.


title: Single-cell RNA expression profiling of ACE2 and AXL in the human maternal-Fetal interface

text: 2019 novel coronavirus disease has resulted in thousands of critically ill patients in China, which is a serious threat to people's life and health. Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was reported to share the same receptor, angiotensin-converting enzyme 2 (ACE2), with SARS-CoV. Here, based on the public single-cell RNA-sequencing database, we analyzed the mRNA expression profile of putative receptor ACE2 and AXL receptor tyrosine kinase (AXL) in the early maternal-fetal interface. The result indicates that the ACE2 has very low expression in the different cell types of early maternal-fetal interface, except slightly high in decidual perivascular cells cluster 1 (PV1). Interestingly, we found that the Zika virus (ZIKV) receptor AXL expression is concentrated in perivascular cells and stromal cells, indicating that there are relatively more AXL-expressing cells in the early maternal-fetal interface. This study provides a possible infection route and mechanism for the SARS-CoV-2- or ZIKV-infected mother-to-fetus transmission disease, which could be informative for future therapeutic strategy development. Zheng Qing-Liang 1 Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204 Duan Tao 2 Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204 Jin Li-Ping 3 Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204 Wang W, Tang J, Wei F. Updated understanding of the outbreak of 2019 novel coronavirus (2019-nCoV) in Wuhan, China. J Med Virol 2020. [Ahead of print]. doi: 10.1002/jmv.25689. Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: A retrospective review of medical records. Lancet 2020. [Ahead of print]. doi: 10.1016/S0140-6736(20) 30360-3. Xu X, Chen P, Wang J, Feng J, Zhou H, Li X, et al. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci China Life Sci 2020. [Ahead of print]. doi: 10.1007/s11427-020-1637-5. Li W, Sui J, Huang IC, Kuhn JH, Radoshitzky SR, Marasco WA, et al. The S proteins of human coronavirus NL63 and severe acute respiratory syndrome coronavirus bind overlapping regions of ACE2. Virology 2007;367:367-74. doi: 10.1016/j.virol.2007.04.035. Ferreira LM, Meissner TB, Tilburgs T, Strominger JL. HLA-G: At the interface of maternal-fetal tolerance. Trends Immunol 2017;38:272-86. doi: 10.1016/j.it.2017.01.009. Picelli S, Faridani OR, Björklund AK, Winberg G, Sagasser S, Sandberg R. Full-length RNA-seq from single cells using Smart-seq2. Nat Protoc 2014;9:171-81. doi: 10.1038/nprot.2014.006. Vento-Tormo R, Efremova M, Botting RA, Turco MY, Vento-Tormo M, Meyer KB, et al. Single-cell reconstruction of the early maternal-fetal interface in humans. Nature 2018;563:347-53. doi: 10.1038/s41586-018-0698-6. Zhao Y, Zhao Z, Wang Y, Zhou Y, Ma Y, Zuo W. Single-cell RNA expression profiling of ACE2, the putative receptor of Wuhan 2019-nCov. BioRxiv 2020. [Ahead of print]. doi: 10.1101/2020.01.26.919985. Lazear HM, Diamond MS. Zika virus: New clinical syndromes and its emergence in the western hemisphere. J Virol 2016;90:4864-75. doi: 10.1128/JVI.00252-16. Petersen LR, Jamieson DJ, Powers AM, Honein MA. Zika virus. N Engl J Med 2016;374:1552-63. doi: 10.1056/NEJMra1602113. Rasmussen SA, Jamieson DJ, Honein MA, Petersen LR. Zika virus and birth defects - Reviewing the evidence for causality. N Engl J Med 2016;374:1981-7. doi: 10.1056/NEJMsr1604338. Brasil P, Pereira JP Jr., Moreira ME, Ribeiro Nogueira RM, Damasceno L, Wakimoto M, et al. Zika virus infection in pregnant women in Rio de Janeiro. N Engl J Med 2016;375:2321-34. doi: 10.1056/NEJMoa1602412. Tabata T, Petitt M, Puerta-Guardo H, Michlmayr D, Wang C, Fang-Hoover J, et al. Zika virus targets different primary human placental cells, suggesting two routes for vertical transmission. Cell Host Microbe 2016;20:155-66. doi: 10.1016/j.chom.2016.07.002. Quicke KM, Bowen JR, Johnson EL, McDonald CE, Ma H, O'Neal JT, et al. Zika virus Infects Human Placental Macrophages. Cell Host Microbe 2016;20:83-90. doi: 10.1016/j.chom.2016.05.015.


title: Crystal structure of inhibitor-bound human MSPL that can activate high pathogenic avian influenza

text: Viral infection is triggered when a surface envelope glycoprotein, hemagglutinin (HA), is cleaved by host cell proteins of the transmembrane protease serine (TMPRSS) family. The extracellular region of TMPRSS-2, -3, -4, and MSPL are composed of LDLA, SRCR, and SPD domains. MSPL can cleave the consensus multibasic (R-X-X/R-R) and monobasic (Q(E)-T/X-R) motifs on HA, while TMPRSS2 or -4 only cleaves monobasic motifs. To better understand HA cleavage mediated by MSPL, we solved the crystal structure of the extracellular region of human MSPL in complex with the furin inhibitor. The structure revealed that three domains are gathered around the C-terminal α-helix of the SPD domain. The furin inhibitor structure shows that the side chain of P1-Arg inserts into the highly conserved S1 pocket, whereas the side chain of P2-Lys interacts with the Asp/Glu-rich 99 loop that is unique to MSPL. We also constructed a homology model of TMPRSS2, which is identified as an initiator of SARS-CoV-2 infection. The model suggests that TMPRSS2 is more suitable for Ala/Val residues at the P2 site than Lys/Arg residues.


title: The proportion testing positive for SARS-COV-2 among the tested population in the U.S.: Benefits of the positive test ratio under scaled testing scenarios

text: The ratios offer simple ways to account for variations in testing and reporting. Tracking the ratios in addition to cases offer a more precise view of the pandemic. Our observations underscore the need to scale mass testing with accurate and reliable tests, to implement testing systematically and report results consistently.


Infectious diseases and football–lessons not only from COVID-19


title: Information about COVID-19 and the liver

text: Unknown