title: A potent neutralizing human antibody reveals the N-terminal domain of the Spike protein of SARS-CoV-2 as a site of vulnerability

text: The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a global public health threat. Most research on therapeutics against SARS-CoV-2 focused on the receptor binding domain (RBD) of the Spike (S) protein, whereas the vulnerable epitopes and functional mechanism of non-RBD regions are poorly understood. Here we isolated and characterized monoclonal antibodies (mAbs) derived from convalescent COVID-19 patients. An mAb targeting the N-terminal domain (NTD) of the SARS-CoV-2 S protein, named 4A8, exhibits high neutralization potency against both authentic and pseudotyped SARS-CoV-2, although it does not block the interaction between angiotensin-converting enzyme 2 (ACE2) receptor and S protein. The cryo-EM structure of the SARS-CoV-2 S protein in complex with 4A8 has been determined to an overall resolution of 3.1 Angstrom and local resolution of 3.4 Angstrom for the 4A8-NTD interface, revealing detailed interactions between the NTD and 4A8. Our functional and structural characterizations discover a new vulnerable epitope of the S protein and identify promising neutralizing mAbs as potential clinical therapy for COVID-19.


title: Surveillance by age-class and prefecture for emerging infectious febrile diseases with respiratory symptoms, including COVID−19

text: Object The COVID-19 outbreak emerged in late 2019 in China, expanding rapidly thereafter. Even in Japan, epidemiological linkage of transmission was probably lost already by February 18, 2020. From that time, it has been necessary to detect clusters using syndromic surveillance. Method We identified common symptoms of COVID-19 as fever and respiratory symptoms. Therefore, we constructed a model to predict the number of patients with antipyretic analgesics (AP) and multi-ingredient cold medications (MIC) controlling well-known pediatric infectious diseases including influenza or RS virus infection. To do so, we used the National Official Sentinel Surveillance for Infectious Diseases (NOSSID), even though NOSSID data are weekly data with 10 day delays, on average. The probability of a cluster with unknown febrile disease with respiratory symptoms is a product of the probabilities of aberrations in AP and MIC, which is defined as one minus the probability of the number of patients prescribed a certain type of drug in PS compared to the number predicted using a model. This analysis was conducted prospectively in 2020 using data from October 1, 2010 through 2019 by prefecture and by age-class. Results The probability of unknown febrile disease with respiratory symptom cluster was estimated as less than 60% in 2020. Discussion The most severe limitation of the present study is that the proposed model cannot be validated. A large outbreak of an unknown febrile disease with respiratory symptoms must be experienced, at which time, practitioners will have to wing it. We expect that no actual cluster of unknown febrile disease with respiratory symptoms will occur, but if it should occur, we hope to detect it.


title: COVID-19 case forecasting model for Sri Lanka based on Stringency Index

text: Introduction Sri Lanka has been able to contain COVID-19 transmission through very stringent suppression measures implemented from the onset. The country had been under a strict lockdown since 20 March 2020, and currently the lockdown is being relaxed gradually. The objective of this paper is to describe a projection model for COVID-19 cases in Sri Lanka applied to different scenarios after lockout, utilizing the stringency index as a proxy of total government response. Methods COVID-19 Stringency Index (C19SI) is published and updated real time by a research group from Oxford university on 17 selected mitigation and suppression measures employed by different countries. We have mapped and validated the stringency index for Sri Lanka and subsequently validated the projection model in two phases. Predictions for the base-case scenario, less stringent scenarios, advanced relaxation scenarios, and high-risk districts were done with 95% confidence intervals (95%CI) using the validated model, utilizing data up to 10th May. Results C19SI was able to accommodate all of the government responses. The model using validated C19SI could predict number of cases with 95% confidence for a period of two weeks. The model predicted base-case scenario of 815 (95%CI, 753-877) active cases by 17 May 2020 and 648 (95%CI, 599-696) cases for the high-risk districts by 18 May 2020. The model further predicted 3,159 (95%CI, 2,928-3,391) cases for 75% stringency and 928,824 (95%CI, 861,772-995,877) cases for 50% stringency. Advancing normalcy by three weeks resulted in the case load increasing to 4526 (95%CI, 4309-4744) by 30 June 2020. Conclusion The proposed prediction model based on C19SI provides policy makers an evidence based scientific method for identifying suppression measures that can be relaxed at the most appropriate time. Key words: COVID-19, Projections, Stringency Index, SIR Model, Sri Lanka


title: Evaluation of serological tests for SARS-CoV-2: Implications for serology testing in a low-prevalence setting

text: Background: Robust serological assays are essential for long-term control of the COVID-19 pandemic. Many recently released point-of-care (PoCT) serological assays have been distributed with little pre-market validation. Methods: Performance characteristics for five PoCT lateral flow devices approved for use in Australia were compared to a commercial enzyme immunoassay (ELISA) and a recently described novel surrogate virus neutralisation test (sVNT). Results: Sensitivities for PoCT ranged from 51.8% (95% CI 43.1 to 60.4%) to 67.9% (95% CI 59.4-75.6%), and specificities from 95.6% (95% CI 89.2-98.8%) to 100.0% (95% CI 96.1-100.0%). Overall ELISA sensitivity for either IgA or IgG detection was 67.9% (95% CI 59.4-75.6), increasing to 93.8% (95% CI 85.0-98.3%) for samples >14 days post symptom onset. Overall, sVNT sensitivity was 60.9% (95% CI 53.2-68.4%), rising to 91.2%% (95% CI 81.8-96.7%) for samples collected >14 days post-symptom onset, with a specificity 94.4% (95% CI 89.2-97.5%), Conclusion: Performance characteristics for COVID-19 serological assays were generally lower than those reported by manufacturers. Timing of specimen collection relative to onset of illness or infection is crucial in the reporting of performance characteristics for COVID-19 serological assays. The optimal algorithm for implementing serological testing for COVID-19 remains to be determined, particularly in low-prevalence settings.


title: TWIRLS, an automated topic-wise inference method based on massive literature, suggests a possible mechanism via ACE2 for the pathological changes in the human host after coronavirus infection

text: Faced with the current large-scale public health emergency, collecting, sorting, and analyzing biomedical information related to the "coronavirus" should be done as quickly as possible to gain a global perspective, which is a basic requirement for strengthening epidemic control capacity. However, for human researchers studying the viruses and the hosts, the vast amount of information available cannot be processed effectively and in a timely manner, particularly when the scientific understanding may be limited, which can further lower the information processing efficiency. We present TWIRLS, a method that can automatically acquire, organize, and classify information. Additionally, independent functional data sources can be added to build an inference system using a machine-based approach, which can provide relevant knowledge to help human researchers quickly establish subject cognition and to make more effective decisions. TWIRLS can automatically analyze more than three million words in more than 14,000 literature articles in only 4 hours. Combining with generalized gene interaction databases creates a data interface that can help researchers to further analyze the information. Using the TWIRLS system, we found that an important regulatory factor angiotensin-converting enzyme 2 (ACE2) may be involved in the host pathological changes on binding to the coronavirus after infection. After triggering functional changes in ACE2/AT2R, an imbalance in the steady-state cytokine regulatory axis involving the Renin-Angiotensin System and IP-10 leads to a cytokine storm.


title: COVID-19: Taiwan’s epidemiological characteristics and public and hospital responses

text: BACKGROUND: Coronavirus disease 19 (COVID-19) is a global health threat with significant medical, economic, social and political implications. The optimal strategies for combating COVID-19 have not been fully determined and vary across countries. METHODS: By the end of February 2020 in Taiwan, 2,150 patients received diagnostic COVID-19 testing and 39 confirmed cases were detected. This is a relatively lower rate of infection compared to other Asian countries. In this article, we summarize the epidemiological characteristics of the 39 infected patients as well as public and hospital responses to COVID-19. RESULTS: Thirty-nine COVID-19 cases and one death have been confirmed in Taiwan. Seventeen of these patients were infected by family members or in hospital wards, emphasizing how COVID-19 is mostly spread by close contact. We examined how hospital have responded to COVID-19, including their implementation of patient route control, outdoor clinics, hospital visit restrictions and ward and staff modifications. We also studied the public’s use of face masks in response to COVID-19. These strategies may reduce the spread of COVID-19 in other countries. CONCLUSION: The emergence and spread of COVID-19 is a threat to health worldwide. Taiwan has reported lower infected cases and its strategies may contribute to further disease prevention and control.


title: Asymptomatic COVID-19 Have Longer Treatment Cycle Than Moderate Type of Confirmed Patients

text: IMPORTANCE A kind of pneumonia caused by unknown causes that occurred in Wuhan, Hubei, China in December 2019, was reported as a result of novel coronavirus infection on January 7, 2020, and then WHO named it "COVID-19". The comparison of epidemiological and clinical characteristics for those patients between asymptomatic COVID-19 infections and moderate type of confirmed cases is limited. OBJECTIVE To compare the difference of epidemiology and clinical characteristics between asymptomatic COVID-19 infections and moderate type of confirmed cases. DESIGN, SETTING, AND PARTICIPANTS Retrospective, single-center cohort study of COVID-19 involving 52 infections of both 26 asymptomatic and 26 moderate type of confirmed cases in the recovery stage at Guizhou Provincial Staff Hospital in Guiyang, China, from January 29, to March 31, 2020; final date of follow-up was April 22. This study was registered in Chinese Clinical Trial Registry Center. EXPOSURES Documented the asymptomatic COVID-19 infections and moderate type of confirmed cases. MAIN OUTCOMES AND MEASURES Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Epidemiological and clinical characteristics of asymptomatic COVID-19 infections and moderate type of confirmed cases were compared. RESULTS The median treatment cycle of asymptomatic COVID-19 infections was 16 days (interquartile range, 11-20 days) and longer than 13 days (interquartile range, 10-15 days) of moderate type of confirmed cases (p=0.049). The median incubation period of asymptomatic COVID-19 infections was 10 days (interquartile range, 0-21 days), while the control group was 7 days (interquartile range, 1-15 days) (p=0.27). On the initial chest computerized tomography (CT) check, 18 (69.2%, 18/26) asymptomatic COVID-19 infections were no imaging changes, which was of no significance compared with 12 (46.2%, 12/26) patients with moderate type of confirmed patients (p=0.092). CONCLUSIONS AND RELEVANCE In this single-center study, we found that asymptomatic COVID-19 infections have longer treatment cycle than those moderate type of confirmed cases.


title: Investigating the social, economic and political consequences of the COVID-19 pandemic: A rolling cross-section approach

text: In this article, we present an application of the rolling cross-section (RCS) design to monitor changes in public opinion during the COVID-19 pandemic in Italy (ResPOnsE Covid-19 project, University of Milan Statale). The RCS is a dynamic survey tool used predominantly in the analyses of public opinion during electoral campaigns. Because of its dynamic nature, we argue that it is an ideal instrument to monitor public opinion during a pandemic. Specifically, we present an RCS online survey implemented in Italy from April to July 2020 and we present some illustrative analyses of changes in behaviors, attitudes, and opinions during the Covid-19 crisis to highlight the potential of the design. Ultimately, we assert that RCS surveys could be very powerful instruments to inform policy makers of the dynamics of public opinion during a crisis, especially when inserted within existent high-quality survey infrastructures.


docid: hypivkho

title: Optimizing the trauma resuscitation bay during the covid-19 pandemic

text: The covid-19 global pandemic due to the SARS-CoV2 (CoV2) virus has created the need to adapt hospital workspaces and staffing models, and trauma is no exception. While the optimal configuration of a trauma resuscitation area is debatable, the space needs to be large enough to accommodate the trauma team and ancillary staff. It also needs to have ready access to supplies and equipment to quickly and easily control hemorrhage, secure an airway and initiate fluid resuscitation. Lastly, stores of personal protective equipment in the form of fluid resistant gowns, head covering, face shield, and gloves (both sterile and non-sterile) should be readily available but under strict access. As CoV2 carriers increased in our population in New Jersey, we treated each incoming trauma patient as a potentially CoV2-positive case and sought to reconfigure out trauma resuscitation area to minimize exposure of our supplies to aerosolized virus.


title: An overview of COVID-19 for diagnostic pathologists: clinicopathological correlation and diagnostic techniques

text: The emergence of COVID-19 as a global pandemic has led to a rapid focus on understanding its pathobiology The constellation of clinical, histological and laboratory findings seen in these patients is similar to other forms of viral pneumonia, but somewhat distinctive aspects exist which may raise the index of suspicion for this disease The pathological findings are not limited to the respiratory system;cardiovascular, gastrointestinal and renal abnormalities have also been described Establishing a link between the clinical features and macroscopic and microscopic findings is not only important for the practicing autopsy pathologist, but also for understanding of the disease as a whole Furthermore, context-sensitive interpretation of diagnostic tests is essential This article aims to review understanding of clinicopathological correlation in COVID-19, as well as clarifying the role of current diagnostic techniques


title: Single-cell transcriptional atlas of the Chinese horseshoe bat (Rhinolophus sinicus) provides insight into the cellular mechanisms which enable bats to be viral reservoirs

text: Bats are a major “viral reservoir” in nature and there is a great interest in not only the cell biology of their innate and adaptive immune systems, but also in the expression patterns of receptors used for cellular entry by viruses with potential cross-species transmission. To address this and other questions, we created a single-cell transcriptomic atlas of the Chinese horseshoe bat (Rhinolophus sinicus) which comprises 82,924 cells from 19 organs and tissues. This atlas provides a molecular characterization of numerous cell types from a variety of anatomical sites, and we used it to identify clusters of transcription features that define cell types across all of the surveyed organs. Analysis of viral entry receptor genes for known zoonotic viruses showed cell distribution patterns similar to that of humans, with higher expression levels in bat intestine epithelial cells. In terms of the immune system, CD8+ T cells are in high proportion with tissue-resident memory T cells, and long-lived effector memory nature killer (NK) T-like cells (KLRG1, GZMA and ITGA4 genes) are broadly distributed across the organs. Isolated lung primary bat pulmonary fibroblast (BPF) cells were used to evaluate innate immunity, and they showed a weak response to interferon β and tumor necrosis factor-α compared to their human counterparts, consistent with our transcriptional analysis. This compendium of transcriptome data provides a molecular foundation for understanding the cell identities, functions and cellular receptor characteristics for viral reservoirs and zoonotic transmission.


title: Estimating the Impact of Control Measures to Prevent Outbreaks of COVID-19 Associated with Air Travel into a COVID-19-free country: A Simulation Modelling Study

text: Aims: We aimed to estimate the risk of COVID-19 outbreaks associated with air travel from a country with a very low prevalence of COVID-19 infection (Australia) to a COVID-19-free country (New Zealand; [NZ]), along with the likely impact of various control measures for passengers and cabin crew. Methods: A stochastic version of the SEIR model CovidSIM v1.1, designed specifically for COVID-19 was utilized. It was populated with data for both countries and parameters for SARS-CoV-2 transmission and control measures. We assumed one Australia to NZ flight per day. Results: When no interventions were in place, an outbreak of COVID-19 in NZ was estimated to occur after an average time of 1.7 years (95% uncertainty interval [UI]: 0.04-6.09). However, the combined use of exit and entry screening (symptom questionnaire and thermal camera), masks on aircraft and two PCR tests (on days 3 and 12 in NZ), combined with self-reporting of symptoms and contact tracing and mask use until the second PCR test, reduced this risk to one outbreak every 29.8 years (0.8 to 110). If no PCR testing was performed, but mask use was used by passengers up to day 15 in NZ, the risk was one outbreak every 14.1 years. However, 14 days quarantine (NZ practice in May 2020), was the most effective strategy at one outbreak every 34.1 years (0.06 to 125); albeit combined with exit screening and mask use on flights. Conclusions: Policy-makers can require multi-layered interventions to markedly reduce the risk of importing the pandemic virus into a COVID-19-free nation via air travel. There is potential to replace 14-day quarantine with PCR testing or interventions involving mask use by passengers in NZ. However, all approaches require continuous careful management and evaluation.


title: Impact of COVID-19 Second Wave on Healthcare Networks in the United States

text: The risk of overwhelming healthcare systems from a second wave of COVID-19 is yet to be quantified. Here, we investigate the impact of different reopening scenarios of states around the U.S. on COVID-19 hospitalized cases and the risk of overwhelming the healthcare system while considering resources at the county level. We show that the second wave might involve an unprecedented impact on the healthcare system if an increasing number of the population becomes susceptible and/or if the various protective measures are discontinued. Furthermore, we explore the ability of different mitigation strategies in providing considerable relief to the healthcare system. The results can aid healthcare planners, policymakers, and state officials in making decisions on additional resources required and on when to return to normalcy.


title: Clinical Characteristics of 2019 Novel Infected Coronavirus Pneumonia：A Systemic Review and Meta-analysis

text: Background:A Novel pneumonia associated with the 2019 coronavirus infected pneumonia (NCIP) suddenly broke out in Wuhan, China in December 2019. 37287 confirmed cases and 813 death case in China (Until 8th/Feb/2019) have been reported in just fortnight. Although this risky pneumonia with high infection rates and high mortality rates need to be resolved immediately, major gaps in our knowledge of clinical characters of it were still not be established. The aim of this study is to summaries and analysis the clinical characteristics of 2019-nCoV pneumonia. Methods: Literature have been systematically performed a search on PubMed, Embase, Web of Science, GreyNet International, and The Cochrane Library from inception up to February 8, 2020. The Newcastle-Ottawa Scale was used to assess quality, and publication bias was analyzed by Egger test. In the single-arm meta-analysis, A fix-effects model was used to obtain a pooled incidence rate. We conducted subgroup analysis according to geographic region and research scale. Results: A total of nine studies including 356 patients were included in this study, the mean age was 52.4 years and 221 (62.1%) were male. The pooled incidences rate of symptoms as follows: pharyngalgia (12.2%, 95% CI: 0.087-0.167), diarrhea (9.2%, 95% CI: 0.062-0.133) and headache (8.9%, 95% CI: 0.063-0.125). Meanwhile, 5.7% (95% CI: 0.027-0.114) of patients were found without any symptoms although they were diagnosed by RT-PCR. In the terms of CT imaging examination, the most of patients showed bilateral mottling or ground-glass opacity, 8.6% (95% CI: 0.048-0.148) of patients with crazy-paving pattern, and 11.5% (95% CI: 0.064-0.197) of patients without obvious CT imaging presentations. The pooled incidence of mortality was 8.9% (95% CI: 0.062-0.126). Conclusions: To our knowledge, this is the first evidence-based medicine research to further elaborate the clinical characteristics of NCIP, which is beneficial to the next step of prevention and treatment.


title: Remdesivir use in patients with coronavirus COVID-19 disease: a systematic review and meta-analysis

text: Background Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2, has led to significant global mortality and morbidity. Until now, no treatment has proven to be effective in COVID-19. To explore whether the use of remdesivir, initially an experimental broad-spectrum antiviral, is effective in the treatment of hospitalized patients with COVID-19, we conducted a systematic review and meta-analysis of randomized, placebo-controlled trials investigating its use. Methods A rapid search of the MEDLINE and EMBASE medical databases was conducted for randomized controlled trials. A systematic approach was used to screen, abstract, and critically appraise the studies. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method was applied to rate the certainty and quality of the evidence reported per study. Results Two RCTs studies were identified (n=1,299). A fixed-effects meta-analysis revealed reductions in mortality (RR=0.69, 0.49 to 0.99), time to clinical improvement (3.95 less days, from 3.86 days less to 4.05 less days ), serious adverse events (RR=0.77, 0.63 to 0.94) and all adverse events (RR=0.87, 0.79 to 0.96). Conclusion In this rapid systematic review, we present pooled evidence from the 2 included RCT studies that reveal that remdesivir has a modest yet significant reduction in mortality and significantly improves the time to recovery, as well as significantly reduced risk in adverse events and serious adverse events. It is more than likely that as an antiviral, remdesivir is not sufficient on its own and may be suitable in combination with other antivirals or treatments such as convalescent plasma. Research is ongoing to clarify and contextual these promising findings.


title: Repeat SARS-CoV-2 Testing Models for Residential College Populations

text: Residential colleges are considering re-opening under uncertain futures regarding the COVID-19 pandemic. We consider repeat SARS-CoV-2 testing models for the purpose of containing outbreaks in the residential campus community. The goal of repeat testing is to rapidly detect and isolate new infections as they occur to block transmission that would otherwise occur on campus and, of arguably greater importance, off. The models allow for the evolution of test sensitivity with time from infection, scheduled on-campus resident screening at a given frequency, imported infections from off campus throughout the school year, and a lag from testing until student isolation due to laboratory turnaround and student relocation delay. For early- (late-) transmission of SARS-CoV-2 by age of infection, we find that weekly screening cannot reliably contain outbreaks with reproductive numbers above 1.4 (1.6) if more than one imported exposure per 10,000 students occurs daily. Screening every three days can contain outbreaks providing the reproductive number remains below 1.75 (2.3) if transmission happens earlier (later) with time from infection, but at the cost of greatly increased false positive rates requiring more isolation quarters for students testing positive. Testing frequently while minimizing the delay from testing until isolation for those found positive are the most controllable levers for preventing large residential college outbreaks.


title: Identification of super-transmitters of SARS-CoV-2

text: A newly emerged coronavirus, SARS-CoV-2, caused severe outbreaks of pneumonia in China in December 2019 and has since spread to various countries around the world. To probe the origin and transmission dynamics of this virus, we performed phylodynamic analysis of 247 high quality genomic sequences of viruses available in the GISAID platform as of March 05, 2020. A substantial number of earliest sequences reported in Wuhan in December 2019, including those of viruses recovered from the Huanan Seafood Market (HNSM), the site of the initial outbreak, were genetically diverse, suggesting that viruses of multiple sources were involved in the original outbreak. The viruses were subsequently disseminated to different parts of China and other countries, with diverse mutational profiles being recorded in strains recovered subsequently. Interestingly, four genetic clusters defined as Super-transmitters (STs) were found to become dominant and were responsible for the major outbreaks in various countries. Among the four clusters, ST1 is widely disseminated in Asia and the US and mainly responsible for outbreaks in the states of Washington and California in the US as well as those in South Korea at the end of February and early March, whereas ST4 contributed to the pandemic in Europe. Each ST cluster carried a signature mutation profile which allowed us to trace the origin and transmission patterns of specific viruses in different parts of the world. Using the signature mutations as markers of STs, we further analysed 1539 genome sequences reported after February 29, 2020. We found that around 90% of these genomes belonged to STs with ST4 being the dominant one and their contribution to pandemic in different continents were also depicted. The identification of these super-transmitters provides insight into the control of further transmission of SARS-CoV-2.


title: A Novel Triage Tool of Artificial Intelligence Assisted Diagnosis Aid System for Suspected COVID-19 pneumonia In Fever Clinics

text: Currently, the prevention and control of COVID-19 outside Hubei province in China, and other countries has become more and more critically serious. We developed and validated a diagnosis aid model without CT images for early identification of suspected COVID-19 pneumonia (S-COVID-19-P) on admission in adult fever patients and made the validated model available via an online triage calculator. Patients admitted from Jan 14 to Feb 26, 2020 with the epidemiological history of exposure to COVID-19 were included [Model development (n = 132) and validation (n = 32)]. Candidate features included clinical symptoms, routine laboratory tests and other clinical information on admission. Features selection and model development were based on Lasso regression. The primary outcome is the development and validation of a diagnosis aid model for S-COVID-19-P early identification on admission. The development cohort contains 26 S-COVID-19-P and 7 confirmed COVID-19 pneumonia cases. The model performance in held-out testing set and validation cohort resulted in AUCs of 0.841 and 0.938, F-1 score of 0.571 and 0.667, recall of 1.000 and 1.000, specificity of 0.727 and 0.778, and the precision of 0.400 and 0.500. Based on this model, an optimized strategy for S-COVID-19-P early identification in fever clinics has also been designed. S-COVID-19-P could be identified early by a machine-learning model only used collected clinical information without CT images on admission in fever clinics with 100% recall score. The well performed and validated model has been deployed as an online triage tool, which is available at: https://intensivecare.shinyapps.io/COVID19/.


An Extended Statement by the British Cardiovascular Intervention Society President Regarding the COVID-19 Pandemic


title: Machine learning model estimating number of COVID-19 infection cases over coming 24 days in every province of South Korea (XGBoost and MultiOutputRegressor)

text: We built a machine learning model (ML model) which input the number of daily infection cases and the other information related to COVID-19 over the past 24 days in each of 17 provinces in South Korea, and output the total increase in the number of infection cases in each of 17 provinces over the coming 24 days. We employ a combination of XGBoost and MultiOutputRegressor as machine learning model (ML model). For each province, we conduct a binary classification whether our ML model can classify provinces where total infection cases over the coming 24 days is more than 100. The result is Sensitivity = 3/3 = 100%, Specificity = 11/14 = 78.6%, False Positive Rate = 3/11 = 21.4%, Accuracy = 14/17 = 82.4%. Sensitivity = 100% means that we did not overlook the three provinces where the number of COVID-19 infection cases increased by more than100. In addition, as for the provinces where the actual number of new COVID-19 infection cases is less than 100, the ratio (Specificity) that our ML model can correctly estimate was 78.6%, which is relatively high. From the above all, it is demonstrated that there is a sufficient possibility that our ML model can support the following four points. (1) Promotion of behavior modification of residents in dangerous areas, (2) Assistance for decision to resume economic activities in each province, (3) Assistance in determining infectious disease control measures in each province, (4) Search for factors that are highly correlated with the future increase in the number of COVID-19 infection cases.


title: Monitoring and Tracking the Evolution of a Viral Epidemic Through Nonlinear Kalman Filtering: Application to the Covid-19 Case

text: This work presents a novel methodology for systematically processing the time series that report the number of positive, recovered and deceased cases from a viral epidemic, such as Covid-19. The main objective is to unveil the evolution of the number of real infected people, and consequently to predict the peak of the epidemic and subsequent evolution. For this purpose, an original nonlinear model relating the raw data with the time-varying geometric ratio of infected people is elaborated, and a Kalman Filter is used to estimate the involved state variables. A hypothetical simulated case is used to show the adequacy and limitations of the proposed method. Then, several countries, including China, South Korea, Italy, Spain, UK and the USA, are tested to illustrate its behavior when real-life data are processed. The results obtained clearly show the beneficial effect of the social distancing measures adopted worldwide, confirming that the Covid-19 epidemic peak is left behind in those countries where the outbreak started earlier, and anticipating when the peak will take place in the remaining countries.


title: Generalized anxiety disorder, depressive symptoms and sleep quality during COVID-19 epidemic in China: a web-based cross-sectional survey

text: Background: China has been severely affected by COVID-19 (Corona Virus Disease 2019) since December, 2019. This study aimed to assess the population mental health burden during the epidemic, and to explore the potential influence factors. Methods: Using a web-based cross-sectional survey, we collected data from 7,236 self-selected volunteers assessed with demographic information, COVID-19 related knowledge, Generalized Anxiety Disorder-7 (GAD-7), Center for Epidemiology Scale for Depression (CES-D), and Pittsburgh Sleep Quality Index (PSQI). Logistic regressions were used to identify influence factors associated with mental health problem. Results: Of the total sample analyzed, the overall prevalence of GAD, depressive symptoms, and sleep quality were 35.1%, 20.1%, and 18.2%, respectively. Young people reported a higher prevalence of GAD and depressive symptoms than older people (P<0.001). Compared with other occupational group, healthcare workers have the highest rate of poor sleep quality (P<0.001). Multivariate logistic regression showed that age (< 35 years) and times to focus on the COVID-19 (≥ 3 hours per day) were associated with GAD, and healthcare workers were associated with poor sleep quality. Conclusions: Our study identified a major mental health burden of the public during COVID-19 epidemic in China. Young people, people who spent too much time on the epidemic, and healthcare workers were at high risk for mental illness. Continuous surveillance and monitoring of the psychological consequences for outbreaks should become routine as part of preparedness efforts worldwide.


title: Ethical comments on COVID-19/ ЭТИЧЕСКИЙ КОММЕНТАРИЙ К COVID-19

text: Over decades, the St. Petersburg Pasteur Institute has been conducting research on Ethical and legal aspects of infectious diseases. One of the areas in this study focuses on ethical issue in the planning and management during epidemics and pandemics. This concept becomes extremely relevant in the situation of the COVID-19 coronavirus pandemic, which has determined the urgent need for rapid updates on this issue and analyzing compliance of decisions and actions undertaken to ethical and legal regulations in Russia and abroad. The rational and practical side of following the global ideology of ethical commitment during worldwide threats due to spread of infectious diseases is aimed to facilitate in preventing violated integrity of anti-epidemic measures, formation of social unity and, finally, to ensure stability of human values, which will be discussed in this study.


title: Controlling the Spread of COVID-19: Optimal Control Analysis

text: Coronavirus disease 2019 (COVID-19) is a disease caused by Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2). It was declared on March 11, 2020, by the World Health Organization as pandemic disease. The disease has neither approved medicine nor vaccine and has made government and scholars search for drastic measures in combating the pandemic. Regrettably, the spread of the virus and mortality due to COVID-19 has continued to increase daily. Hence, it is imperative to control the spread of the disease particularly using non-pharmacological strategies such as quarantine, isolation and public health education. This work studied the effect of these different control strategies as time-dependent interventions using mathematical modeling and optimal control approach to ascertain their contributions in the dynamic transmission of COVID-19. The model was proven to have an invariant region and was well-posed. The basic reproduction number was computed with and without interventions and was used to carry out the sensitivity analysis that identified the critical parameters contributing to the spread of COVID-19. The optimal control analysis was carried out using the Pontryagin maximum principle to figure out the optimal strategy necessary to curtail the disease. The findings of the optimal control analysis and numerical simulations revealed that time-dependent interventions reduced the number of exposed and infected individuals compared to time-independent interventions. These interventions were time-bound and best implemented within the first 100 days of the outbreak. Again, the combined implementation of only two of these interventions produced a good result in reducing infection in the population, while the combined implementation of all three interventions performed better, even though zero infection was not achieved in the population. This implied that multiple interventions need to be deployed early in order to the virus to the barest minimum.


title: Optimistic bias and preventive behavioral engagement in the context of COVID-19

text: Background: The coronavirus (COVID-19) pandemic presents a global crisis. To remain safe, individuals must take preventive measures. Health behavior theories suggest that perceived risk is a key determinant of engagement in preventive behavior. People often underestimate their risk for disease compared with similar others’, a phenomenon known as optimistic bias (OB). Objective: This study aimed to explore how OB affected individuals' engagement in COVID-19 preventive behavior/intentions. Based on health behavior theories, this study considered risk perception and risk response as mediators of the relationship between OB and individuals’ preventive health behaviors and intentions. Methods: This study used a cross-sectional survey design. Online survey platforms were used to recruit U.S. adults. A total of 293 valid responses were included in the analyses. Multivariate regression analyses were conducted to determine the relationship of OB to the respondents’ health information seeking intention and related behavioral outcomes. Results: Results from the first regression model showed that OB was negatively related to risk perception. In other words, optimistically biased respondents perceived their risk of COVID-19 to be low. The second model demonstrated that perceived risk was related positively to affective responses to risk (e.g., worry and fear). That is, the lower their perceived risk of COVID-19, the less likely respondents were to feel anxiety and fear about this disease. Models 3 and 4 revealed positive relationships between risk response and respondents’ intentions and behaviors. Finally, the results supported a fully mediated pathway: OB → risk perception → risk response → information seeking intention and behavioral outcomes. Conclusions: The study findings suggest that by decreasing their perceived risk and subsequent responses, optimistic bias can undermine individuals’ motivation to take precautions. To reduce this bias, the actual risk of COVID-19 should be reinforced.


title: Pain Management Under COVID-19 Coronavirus Infections in Children Including COVID-19: An Overview of the Epidemiology, Clinical Features, Diagnosis, Treatment and Prevention Options in Children

text: Coronaviruses (CoVs) are a large family of enveloped, single-stranded, zoonotic RNA viruses Four CoVs commonly circulate among humans: HCoV2-229E, -HKU1, -NL63 and -OC43 However, CoVs can rapidly mutate and recombine leading to novel CoVs that can spread from animals to humans The novel CoVs severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012 The 2019 novel coronavirus (SARS-CoV-2) is currently causing a severe outbreak of disease (termed COVID-19) in China and multiple other countries, threatening to cause a global pandemic In humans, CoVs mostly cause respiratory and gastrointestinal symptoms Clinical manifestations range from a common cold to more severe disease such as bronchitis, pneumonia, severe acute respiratory distress syndrome, multi-organ failure and even death SARS-CoV, MERS-CoV and SARS-CoV-2 seem to less commonly affect children and to cause fewer symptoms and less severe disease in this age group compared with adults, and are associated with much lower case-fatality rates Preliminary evidence suggests children are just as likely as adults to become infected with SARS-CoV-2 but are less likely to be symptomatic or develop severe symptoms However, the importance of children in transmitting the virus remains uncertain Children more often have gastrointestinal symptoms compared with adults Most children with SARS-CoV present with fever, but this is not the case for the other novel CoVs Many children affected by MERS-CoV are asymptomatic The majority of children infected by novel CoVs have a documented household contact, often showing symptoms before them In contrast, adults more often have a nosocomial exposure In this review, we summarize epidemiologic, clinical and diagnostic findings, as well as treatment and prevention options for common circulating and novel CoVs infections in humans with a focus on infections in children


title: A model of COVID-19 transmission and control on university campuses

text: In response to the COVID-19 pandemic, institutions of higher education in almost every nation closed in the first half of 2020. University administrators are now facing decisions about how to safely return students, staff and faculty to campus. To provide a framework to evaluate various strategies, we developed a susceptible-exposed-infectious-recovered (SEIR) type of deterministic compartmental transmission model of SARS-CoV-2 among students, staff and faculty. Our goals were to support the immediate pandemic planning at our own university, and to provide a flexible modeling framework to inform the planning efforts at similar academic institutions. We parameterized the model for our institution, Emory University, a medium-size private university in Atlanta, Georgia. Control strategies of isolation and quarantine are initiated by screening (regardless of symptoms) or testing (of symptomatic individuals). We explore a range of screening and testing frequencies and perform a probabilistic sensitivity analysis of input parameters. We find that monthly and weekly screening can reduce cumulative incidence by 42% and 80% in students, respectively, while testing with a 2-, 4- and 7-day delay results in an 88%, 79% and 67% reduction in cumulative incidence in students over the semester, respectively. Similar reductions are observed among staff and faculty. A testing strategy requires far fewer diagnostic assays to be implemented than a screening assay. Our intervention model is conservative in that we assume a fairly high reproductive number that is not reduced through social distancing measures. We find that community-introduction of SARS-CoV-2 infection onto campus can be controlled with effective testing, isolation, contract tracing and quarantine, but that cases, hospitalization, and (in some scenarios) deaths may still occur. In addition to estimating health impacts, this model can help to predict the resource requirements in terms of diagnostic capacity and isolation/quarantine facilities associated with different strategies.


title: COVID‐19 associated coagulopathy and thromboembolic disease: Commentary on an interim expert guidance

text: The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV2) is the causative pathogen of a new infectious disease, COVID‐19, that first occurred in late December 2019 in the city of Wuhan in Hubei Province, China. It has since spread globally, resulting in a WHO declared pandemic, with as yet (17/4/20) more than two million confirmed cases and about 150.000 confirmed deaths. As for every new disease, clinicians, hospitals and governments struggle to find optimal clinical and public health measures to contain its spread and burden. For this, information from scientific research is crucial and fortunately we see a rapidly accumulating output of studies.


title: Progression, recovery and fatality in patients with SARS-CoV-2 related pneumonia in Wuhan, China: a single-centered, retrospective, observational study

text: Objectives To determine the case fatality rates and death risk factors. Design Retrospective case series. Setting A COVID-19 ward of a secondary Hospital in Wuhan, China. Participants Consecutively hospitalized COVID-19 patients between Jan 3, 2020 and Feb 27, 2020. Outcomes were followed up to discharge or death. Results Of 121 patients included, 66 (54.6%) were males. The median age was 59 (IQR: 46 to 67) years, and hypertension (33 patients; 27.3%) the leading comorbidity. Lymphopenia (83 of 115 patients; 72.2%) frequently occurred and then normalized on day 4 (IQR: 3 to 6) after admission in the survivors, with lung lesion absorbed gradually on day 8 (IQR: 6 to10) after onset (33 of 57 patients; 57.9%). The real-time polymerase chain reaction (RT-PCR) assays for SARS-CoV-2 were positive in 78 (78/108; 72.2%) patients, and a false-negative RT-PCR occurred in 15 (13.9%) patients. Hypoxemia occurred in 94 (94/117; 80.3%) patients, and supplemental oxygen was given in 88 (72.7%) patients, and mon-invasive or invasive ventilation in 20 (16.5%) cases. Corticosteroid use might link to death. The case fatality rates were 4.4% (one of 23 patients), 29.3% (12/41), 22.8% (13/57) or 45% (9/20) for patients with moderate, severe, critical illness or on ventilator. The length of hospital stay was 14 (IQR: 10 to 20) days, and selfcare ability worsened in 21 patients (21/66; 31.8%) cases. Patients over 60 years were most likely to have poorer outcomes, and increasing in age by one-year increased risk for death by 18% (CI: 1.04-1.32). Conclusions In management of patients with SARS-CoV-2 pneumonia, especially the elderly with hypertension, close monitoring and appropriate supportive treatment should be taken earlier and aggressively to prevent from developing severe or critical illness. Corticosteroid use might link to death. Repeated RT-PCR tests or novel detection methods for SARS-CoV-2 should be adopted to improve diagnostic efficiency.


title: COVID-19 in Seattle – Early Lessons Learned

text: ABSTRACT The coronavirus disease 2019 (COVID-19) pandemic has rapidly evolved and now dominates the attention and full efforts of the emergency medicine community, both domestic and abroad Seattle is the site of the initial diagnosed COVID-19 cases and fatalities in the United States We provide an overview of the system level response of six Seattle emergency departments and the Washington state chapter of the American College of Emergency Physicians (ACEP) to the COVID-19 pandemic Local efforts involved the spectrum of emergency response including on- and off-site triage strategies;an approach to personal protective equipment;testing and reporting protocols;early treatments;communication strategies;the impact on front-line providers;and ongoing work This article is protected by copyright All rights reserved


Breaking News: All We Know about COVID-19 Transmission


COVID-19 Pandemic: What Can We Do as Cosmetic Surgeons?


title: Identification of protein-protected mRNA fragments and structured excised intron RNAs in human plasma by TGIRT-seq peak calling

text: Human plasma contains >40,000 different coding and non-coding RNAs that are potential biomarkers for human diseases. Here, we used thermostable group II intron reverse transcriptase sequencing (TGIRT-seq) combined with peak calling to simultaneously profile all RNA biotypes in apheresis-prepared human plasma pooled from healthy individuals. Extending previous TGIRT-seq analysis, we found that human plasma contains largely fragmented mRNAs from >19,000 protein-coding genes, abundant full-length, mature tRNAs and other structured small non-coding RNAs, and less abundant tRNA fragments and mature and pre-miRNAs. Many of the mRNA fragments identified by peak calling correspond to annotated protein-binding sites and/or have stable predicted secondary structures that could afford protection from plasma nucleases. Peak calling also identified novel repeat RNAs, miRNA-sized RNAs, and putatively structured intron RNAs of potential biological, evolutionary, and biomarker significance, including a family of full-length excised introns RNAs, subsets of which correspond to mirtron pre-miRNAs or agotrons.


title: Detecting the Emergent or Re-Emergent COVID-19 Pandemic in a Country: Modelling Study of Combined Primary Care and Hospital Surveillance

text: Aims: We aimed to determine the effectiveness of surveillance using testing for SARS-CoV-2 to identify an outbreak arising from a single case of border control failure at a country level. Methods: A stochastic version of the SEIR model CovidSIM v1.1 designed specifically for COVID-19 was utilised. It was seeded with New Zealand (NZ) population data and relevant parameters sourced from the NZ and international literature. Results: For what we regard as the most plausible scenario with an effective reproduction number of 2.0, the results suggest that 95% of outbreaks from a single imported case would be detected in the period up to day 33 after introduction. At the time point of detection, there would be a median number of 6 infected cases in the community (95%UI: 1-68). To achieve this level of detection, an on-going programme of 7,800 tests per million people per week for the NZ population would be required. The vast majority of this testing (96%) would be of symptomatic cases in primary care settings and the rest in hospitals. Despite the large number of tests required, there are plausible strategies to enhance testing yield and cost-effectiveness eg, (i) adjusting the eligibility criteria via symptom profiles; (ii) and pooling of test samples. Conclusions: This model-based analysis suggests that a surveillance system with a very high level of routine testing is probably required to detect an emerging or re-emerging SARS-CoV-2 outbreak within one month of a border control failure in a nation.


title: Glycosaminoglycans induce conformational change in the SARS-CoV-2 Spike S1 Receptor Binding Domain

text: The glycosaminoglycan (GAG) class of polysaccharides are utilised by a plethora of microbial pathogens as receptors for adherence and invasion. The GAG heparin prevents infection by a range of viruses when added exogenously, including the S-associated coronavirus strain HSR1 and more recently we have demonstrated that heparin can block cellular invasion by SARS-CoV-2. Heparin has found widespread clinical use as anticoagulant drug and this molecule is routinely used as a proxy for the GAG, heparan sulphate (HS), a structural analogue located on the cell surface, which is a known receptor for viral invasion. Previous work has demonstrated that unfractionated heparin and low molecular weight heparins binds to the Spike (S1) protein receptor binding domain, inducing distinct conformational change and we have further explored the structural features of heparin with regard to these interactions. In this article, previous research is expanded to now include a broader range of GAG family members, including heparan sulphate. This research demonstrates that GAGs, other than those of heparin (or its derivatives), can also interact with the SARS-CoV-2 Spike S1 receptor binding domain and induce distinct conformational changes within this region. These findings pave the way for future research into next-generation, tailor-made, GAG-based antiviral agents, against SARS-CoV-2 and other members of the Coronaviridae.


title: Mass Spectrometric detection of SARS-CoV-2 virus in scrapings of the epithelium of the nasopharynx of infected patients via Nucleocapsid N protein

text: Detection of viral RNA by PCR is currently the main diagnostic tool for COVID-19 [1]. The PCR-based test, however, shows limited sensitivity, especially at early and late stages of the disease development [2,3], and is relatively time consuming. Fast and reliable complementary methods for detecting the viral infection would be of help in the current pandemia conditions. Mass-spectrometry is one of such possibilities. We have developed a mass-spectrometry based method for the detection of the SARS CoV-2 virus in nasopharynx epithelial swabs, based on the detection of the viral nucleocapsid N protein. The N protein of the SARS-COV-2 virus, the most abundant protein in the virion, is the best candidate for mass-spectrometric detection of the infection, and MS-based detection of several peptides from the SARS-COoV-2 nucleoprotein has been reported earlier by the Sinz group [4]. Our approach shows confident identification of the N protein in patient samples even with the lowest viral loads and a much simpler preparation procedure. Our main protocol consists of virus inactivation by heating and adding of isopropanol, and tryptic digestion of the proteins sedimented from the swabs followed by MS analysis. A set of unique peptides, produced as a result of proteolysis of the nucleocapsid phosphoprotein of SARS-CoV-2, is detected. The obtained results can further be used to create fast parallel mass-spectrometric approaches for the detection of the virus in the nasopharyngeal mucosa, saliva, sputum and other physiological fluids.


New Year and coronavirus


title: SARS-CoV-2 seroconversion in health care workers

text: Background The correlates of protection against SARS-CoV-2 and their longevity remain unclear. Studies in severely ill individuals have identified robust cellular and humoral immune responses against the virus. Asymptomatic infection with SARS-CoV-2 has also been described, but it is unknown whether this is sufficient to produce antibody responses. Methods We performed a cross-sectional study recruiting 554 health care workers from University Hospitals Birmingham NHS Foundation Trust who were at work and asymptomatic. Participants were tested for current infection with SARS-CoV-2 by nasopharyngeal swab for real-time polymerase chain reaction and for seroconversion by the measurement of anti-SARS-CoV-2 spike glycoprotein antibodies by enzyme linked immunosorbent assay. Results were interpreted in the context of previous, self-reported symptoms of illness consistent with COVID-19. Results The point prevalence of infection with SARS-CoV-2, determined by the detection of SARS-CoV-2 RNA on nasopharnygeal swab was 2.39% (n=13/544). Serum was available on 516 participants. The overall rate of seroconversion in the cohort was 24.4% (n=126/516). Individuals who had previously experienced a symptomatic illness consistent with COVID-19 had significantly greater seroconversion rates than those who had remained asymptomatic (37.5% vs 17.1%, {chi}2 =21.1034, p<0.0001). In the week preceding peak COVID-19-related mortality at UHBFT, seroconversion rates amongst those who were suffering from symptomatic illnesses peaked at 77.8%. Prior symptomatic illness generated quantitatively higher antibody responses than asymptomatic seroconversion. Seroconversion rates were highest amongst those working in housekeeping (34.5%), acute medicine (33.3%) and general internal medicine (30.3%) with lower rates observed in participants working in intensive care (14.8%) and emergency medicine (13.3%). Conclusions In a large cross-sectional seroprevalence study of health-care workers, we demonstrate that asymptomatic seroconversion occurs, however prior symptomatic illness is associated with quantitatively higher antibody responses. The identification that the potential for seroconversion in health-care workers can associate differentially with certain hospital departments may inform future infection control and occupational health practices.


title: Less Wrong COVID-19 Projections With Interactive Assumptions

text: COVID-19 pandemic is an enigma with uncertainty caused by biological and health systems factors. Although many models have been developed all around the world, transparent models that allow interacting with the assumptions will become more important as we test various strategies for lockdown, testing and social interventions and enable effective policy decisions. In this paper we developed a suite of models to guide development of policies under different scenarios when the lockdown opens. These had been deployed to create an interactive dashboard called COVision which includes the Agent based Models (ABM) and classical compartmental models i.e Susceptible-Infected-Recovered (SIR) and Susceptible-Exposed-Infected-Recovered (SEIR) approaches. Our tool allows simulation of scenarios by changing strength of lockdown, basic reproduction number(R0), asymptomatic spread, testing rate, contact rate (Beta), recovery rate (Gamma), incubation period and starting number of cases. We optimized ABMs and classical compartmental models to fit the actual data, both of which performed well in terms of R-squared, root mean squared error (RMSE) and mean absolute percentage error (MAPE). Out of the three models in our suite, ABM was able to capture the data better than SIR and SEIR and achieved an RSQ of 92.3% for India and 89% for Maharashtra for the next 30 days. We also computed R0 using SIR and SEIR models which were found to be decreasing over the different periods of lockdown indicating the effectiveness of policies and interventions. Finally, we formulated ICU bed requirements using our best models. Our evaluation suggests that ABM models were able to capture the dynamic nature of the epidemic for a longer duration of time while classical SIR and SEIR models performed inefficiently for longer terms. The visual interactivity and ability to simulate outcomes under different parameters will allow the policymakers to make informed decisions for estimating the strength of lockdown to be implemented and testing rates. Further, our models were able to highlight the differences at state level for the parameters such as R0 and contact rates and hence can be applied for state specific decision making. An interactive dashboard http://covision.tavlab.iiitd.edu.in have been hosted as a web-server for the war level monitoring of the covid19 pandemic in India in public domain


docid: vxkbctiz

title: Induction of RNA interference by C. elegans mitochondrial dysfunction via the DRH-1/RIG-I homologue RNA helicase and the EOL-1/RNA decapping enzyme

text: RNA interference (RNAi) is an antiviral pathway common to many eukaryotes that detects and cleaves foreign nucleic acids. In mammals, mitochondrially localized proteins such as MAVS, RIG-I, and MDA5 mediate antiviral responses. Here, we report that mitochondrial dysfunction in Caenorhabditis elegans activates RNAi-directed silencing via induction of a pathway homologous to the mammalian RIG-I helicase viral response pathway. The induction of RNAi also requires the conserved RNA decapping enzyme EOL-1/DXO. The transcriptional induction of eol-1 requires DRH-1 as well as the mitochondrial unfolded protein response (UPRmt). Upon mitochondrial dysfunction, EOL-1 is concentrated into foci that depend on the transcription of mitochondrial RNAs that may form dsRNA, as has been observed in mammalian antiviral responses. The enhanced RNAi triggered by mitochondrial dysfunction contributes to the increase in longevity that is induced by mitochondrial dysfunction.


title: 'Trained immunity' from Mycobacterium spp. exposure or BCG vaccination and COVID-19 outcomes

text: Protective variables for COVID-19 are unknown. 'Trained immunity' of the populace as a result of BCG policy implementation and coverage had been suggested to be one of the factors responsible for the differential impact of COVID-19 on different countries. Several trials are underway to evaluate the potential protective role of BCG vaccination in COVID-19. However, the lack of clarity on the use of appropriate controls concerning 'trained immunity' has been a cause of concern leading to more confusion as exemplified by a recently concluded trial in Israel that failed to find any correlation. Whereas, when we analyze the COVID-19 data of European countries without any mandatory BCG vaccination policy but with similar age distribution, comparable confounding variables, and the stage of the pandemic, the prevalence of Mycobacterium spp.(including BCG vaccine) exposure of the populations is consistently negatively correlated with COVID-19 infections per million population at all the time points evaluated [r(20): -0.5511 to -0.6338; p-value: 0.0118 to 0.0027]. The results indicate that the on-going and future studies evaluating the effect of BCG vaccination on COVID-19 outcomes should consider the inclusion of 'controls' for underlying 'trained immunity' prevalence or that resulting from the intervention (BCG vaccine) in such trials to arrive at more dependable conclusions.


title: Engineered human mesenchymal stem cells as new vaccine platform for COVID-19

text: Recently, there are several routes for COVID-19 vaccine research, yet their weaknesses lie in low efficiency, tolerability, immune adaptability and safety. We describe a new approach to COVID-19 based on engineered human mesenchymal stem cells(hu-MSC), which is like a small protein antigen response device, but will be gradually cleared and degraded by body’s immune system among recognization process. The antibody response results show that this is effective and fast. Furthermore, after several antibody response tests, we obtained an injection of a set of cocktail-like modified human mesenchymal stem cell line. This strategy opened a new avenue for vaccine design against COVID-19.


title: Identifying Non-traditional Epidemic Disease Risk Factors associated to major Health Events from WHO and World Bank Open Data

text: Objectives: Health events emerge from a multifactorial milieu involving host, community, environment, and pathogen factors. Therefore, developing accurate forecasting models to improve epidemic prediction towards better prevention and capabilities management is a complex task. Here, we describe an exploratory analysis to identify non-health risk factors that could improve the forecast and events risk signals using a feasible and practical approach by combining surveillance report data with non-health data from open data sources. Methods: A line listing was developed using information from the World Health Organization Disease Outbreaks News from 2016-2018. A database was created merging the line listing data with non-health indicators from the World Bank. Poisson regression models employing forward imputations were used to establish relationships and predict values over the dependent variable (health event frequency); which are the health events reported by each country to WHO during 2016-2018. Findings: The resulting regression model provided evidence that changes in non-health factors important to community experiences impact the risk of the number of major health events that a country could experience. Three non-health indicators (extrinsic factors) were associated significantly to event frequency (population urban change, gross domestic product change per capita -a novel factor, and average forest area). An exploratory analysis of the current COVID-19 pandemic suggested similar associations, but confounding by global disease burden is likely. Conclusion: Continued development of forecasting approaches capturing available whole-of-society extrinsic factors (non-health factors); could improve the risk management process through earlier hazard identification, and as importantly inform strategic decision processes in multisectoral strategies to preventing, detecting, and responding to pandemic-threat events.


docid: lvqwszsf

title: Structure, function and variants analysis of the androgen-regulated TMPRSS2, a drug target candidate for COVID-19 infection

text: SARS-CoV-2 is a novel virus causing mainly respiratory, but also gastrointestinal symptoms. Elucidating the molecular processes underlying SARS-CoV-2 infection, and how the genetic background of an individual is responsible for the variability in clinical presentation and severity of COVID-19 is essential in understanding this disease. Cell infection by the SARS-CoV-2 virus requires binding of its Spike (S) protein to the ACE2 cell surface protein and priming of the S by the serine protease TMPRSS2. One may expect that genetic variants leading to a defective TMPRSS2 protein can affect SARS-CoV-2 ability to infect cells. We used a range of bioinformatics methods to estimate the prevalence and pathogenicity of TMPRSS2 genetic variants in the human population, and assess whether TMPRSS2 and ACE2 are co-expressed in the intestine, similarly to what is observed in lungs. We generated a 3D structural model of the TMPRSS2 extracellular domain using the prediction server Phyre and studied 378 naturally-occurring TMPRSS2 variants reported in the GnomAD database. One common variant, p.V160M (rs12329760), is predicted damaging by both SIFT and PolyPhen2 and has a MAF of 0.25. Valine 160 is a highly conserved residue within the SRCS domain. The SRCS is found in proteins involved in host defence, such as CD5 and CD6, but its role in TMPRSS2 remains unknown. 84 rare variants (53 missense and 31 leading to a prematurely truncated protein, cumulative minor allele frequency (MAF) 7.34×10−4) cause structural destabilization and possibly protein misfolding, and are also predicted damaging by SIFT and PolyPhen2 prediction tools. Moreover, we extracted gene expression data from the human protein atlas and showed that both ACE2 and TMPRSS2 are expressed in the small intestine, duodenum and colon, as well as the kidneys and gallbladder. The implications of our study are that: i. TMPRSS2 variants, in particular p.V160M with a MAF of 0.25, should be investigated as a possible marker of disease severity and prognosis in COVID-19 and ii. in vitro validation of the co-expression of TMPRSS2 and ACE2 in gastro-intestinal is warranted.


docid: kmucqxyh

title: Study of cell to cell transmission of SARS CoV 2 virus particle using gene network from microarray data

text: Microarray data from SARS CoV2 patients helps to construct a gene network relating to this disease. Analysis of these genes, present in network, highlights their biological functions and related cellular pathways. With the assistance of these information, a drug(s) can be identified to treat COVID-19. A detailed analysis of the human host response to SARS CoV 2 with expression profiling by high throughput sequencing has executed with primary human lung epithelium cell lines. Clustered genes annotation and gene network construction are performed with the help of String database. Among four cluster of genes from microarray data, cluster 1 is identified as basal cells with p= 1.37e−05 with 44 genes. Functional enrichment analysis of genes present in gene network has completed using String database, ToppFun online tool and NetworkAnalyst tool. For SARS CoV2 virus particles, keratin proteins, which are part of cytoskeleton structure of host cell, play a major role in cell to cell virus particle transmission. Among three types of cell- cell communication, only anchoring junction between basal cell membrane and basal lamina, is involved in this virus transmission. In this junction point, hemidesmosome structure play a vital role in virus spread from one cell to basal lamina in respiratory tract. In this protein complex structure, keratin, integrin and laminin proteins of host cell is used to promote the spread of virus infection into extracellular matrix. So, small molecular blockers of different anchoring junction proteins i.e. ITGA3, ITGA2 can provide efficient protection against this deadly virus disease. Understanding the human host response against this virus is very important to develop novel therapeutics for the treatment of SARS-CoV 2.


title: Assessing COVID-19 Risk, Vulnerability and Infection Prevalence in Communities

text: Background: The spread of coronavirus in the United States with nearly one million confirmed cases and over 53,000 deaths has strained public health and health care systems. While many have focused on clinical outcomes, less attention has been paid to vulnerability and risk of infection. In this study, we developed a planning tool that examines factors that affect vulnerability to COVID-19. Methods: Across 46 variables, we defined five broad categories: 1) access to medical, 2) underlying health conditions, 3) environmental exposures, 4) vulnerability to natural disasters, and 5) sociodemographic, behavioral, and lifestyle factors. We also used reported rates for morbidity, hospitalization, and mortality in other regions to estimate risk at the county (Harris County) and census tract levels. Analysis: A principal component analysis was undertaken to reduce the dimensions. Then, to identify vulnerable census tracts, we conducted rank-based exceedance and K-means cluster analyses. Results: Our study showed a total of 722,357 (~17% of the County population) people, including 171,403 between the ages of 45-65 (~4% of County population), and 76,719 seniors (~2% of County population), are at a higher risk based on the aforementioned categories. The exceedance and K-means cluster analysis demonstrated that census tracts in the northeastern, eastern, southeastern and northwestern regions of the County are at highest risk. The results of age-based estimations of hospitalization rates showed the western part of the County might be in greater need of hospital beds. However, cross-referencing the vulnerability model with the estimation of potential hospitalized patients showed that part of the County has the least access to medical facilities. Conclusion: Policy makers can use this planning tool to identify neighborhoods at high risk for becoming hot spots; efficiently match community resources with needs, and ensure that the most vulnerable have access to equipment, personnel, and medical interventions.


Teaching ethnographic methods under COVID-19


title: Seroprevalence of Antibodies to SARS-CoV-2 in Six Sites in the United States, March 23-May 3, 2020

text: Importance: Reported cases of SARS-CoV-2 infection likely underestimate the prevalence of infection in affected communities. Large-scale seroprevalence studies provide better estimates of the proportion of the population previously infected. Objective: To estimate prevalence of SARS-CoV-2 antibodies in convenience samples from several geographic sites in the United States. Design: Serologic testing of convenience samples using residual sera obtained for routine clinical testing by two commercial laboratory companies. Setting: Connecticut (CT), south Florida (FL), Missouri (MO), New York City metro region (NYC), Utah (UT), and Washington State's (WA) Puget Sound region. Participants: Persons of all ages with serum collected during intervals from March 23 through May 3, 2020. Exposure: SARS-CoV-2 virus infection. Main outcomes and measures: We estimated the presence of antibodies to SARS-CoV-2 spike protein using an ELISA assay. We standardized estimates to the site populations by age and sex. Estimates were adjusted for test performance characteristics (96.0% sensitivity and 99.3% specificity). We estimated the number of infections in each site by extrapolating seroprevalence to site populations. We compared estimated infections to number of reported COVID-19 cases as of last specimen collection date. Results: We tested sera from 11,933 persons. Adjusted estimates of the proportion of persons seroreactive to the SARS-CoV-2 spike protein ranged from 1.13% (95% confidence interval [CI] 0.70-1.94) in WA to 6.93% (95% CI 5.02-8.92) in NYC (collected March 23-April 1). For sites with later collection dates, estimates ranged from 1.85% (95% CI 1.00-3.23, collected April 6-10) for FL to 4.94% (95% CI 3.61-6.52) for CT (April 26-May 3). The estimated number of infections ranged from 6 to 24 times the number of reported cases in each site. Conclusions and relevance: Our seroprevalence estimates suggest that for five of six U.S. sites, from late March to early May 2020, >10 times more SARS-CoV-2 infections occurred than the number of reported cases. Seroprevalence and under-ascertainment varied by site and specimen collection period. Most specimens from each site had no evidence of antibody to SARS-CoV-2. Tracking population seroprevalence serially, in a variety of specific geographic sites, will inform models of transmission dynamics and guide future community-wide public health measures.


title: New Horizons: COVID-19 and the Burden of Neuropsychiatric Illness in Pakistan

text: This manuscript reviews the current state of knowledge about the burden of mental illness and assesses the impact of COVID-19 illness on mental health in Pakistan. For this we analyzed secondary data obtained from the Institute of Health Metrics and Evaluation. The Global Burden of Disease (GBD) study draws from a wide range of data sources to quantify global and regional effects of a disease. We also did a literature search on the effects of COVID-19 illness on mental health and the psychosocial effects of COVID-19 and other Corona virus related illnesses such as SARS-CoV and MERS-CoV. Data from the studies obtained was utilized to extrapolate the anticipated effects of COVID-19 illness on healthcare workers, COVID-19 patients and the general public in Pakistan. Mental illness poses a significant challenge to Pakistan’s under resourced health care system. COVID-19 has the potential to strain Pakistan’s healthcare system to the breaking point. So far, the general morbidity from COVID-19 illness in Pakistan has been low compared to other countries but this could change in the coming weeks and months. Hidden within this crisis are also some opportunities for both healthcare and education.


title: Exhaled breath is a significant source of SARS-CoV-2 emission

text: Despite notable efforts in airborne SARS-CoV-2 detection, no clear evidence has emerged to show how SARS-CoV-2 is emitted into the environments. Here, 35 COVID-19 subjects were recruited; exhaled breath condensate (EBC), air samples and surface swabs were collected and analyzed for SARS-CoV-2 using reverse transcription-polymerase chain reaction (RT-PCR). EBC samples had the highest positive rate (16.7%, n=30), followed by surface swabs (5.4%, n=242), and air samples (3.8%, n=26). COVID-19 patients were shown to exhale SARS-CoV-2 into the air at an estimated rate of 103-105 RNA copies/min; while toilet and floor surfaces represented two important SARS-CoV-2 reservoirs. Our results imply that airborne transmission of SARS-CoV-2 plays a major role in COVID-19 spread, especially during the early stages of the disease.


title: A dynamic model for Covid-19 in Brazil.

text: A dynamic model for the current coronavirus outbreak is presented. The most important parameters are identified which determine the number of cases progression. Results of a numerical simulation are compared with existing data of the number of infections in Sao Paulo and Brazil. On the basis of these results measures are proposed to control the epidemics and to flat the infection curve. A simple three steps procedure is proposed to predict the time evolution of the epidemics and a criteria to resume 'normal' activities after quarantine is proposed.


title: The connection of growth and medication of COVID-19 affected people after 30 days of lock down in India

text: The COVID-19 pandemic has already consumed few months of indolence all over the world. Almost every part of the world from which the victim of COVID 19 are, have not yet been able to find out a strong way to combat corona virus. Therefore, the main aim is to minimize the spreading of the COVID-19 by detecting most of the affected people during lockdown. Hence, it is necessary to understand what the nature of growth is of spreading of this corona virus with time after almost one month (30 days) of lockdown. In this paper we have developed a very simple mathematical model to describe the growth of spreading of corona virus in human being. This model is based on realistic fact and the statistics we have so far. For controlling the spread of the COVID-19, minimization of the growth with minimum number of days of lockdown is necessary. We have established a relation between the long-term recovery coefficient and the long-term infected coefficient. The growth can be minimized if such condition satisfies. We have also discussed how the different age of the people can be cured by applying different types of medicine. We have presented the data of new cases, recovery and deaths per day to visualize the different coefficient for India and establish our theory. We have also explained how the medicine could be effective to sustain and improve such condition for country having large population like India.


title: KnetMiner: a comprehensive approach for supporting evidence-based gene discovery and complex trait analysis across species

text: Generating new ideas and scientific hypotheses is often the result of extensive literature and database reviews, overlaid with scientists’ own novel data and a creative process of making connections that were not made before. We have developed a comprehensive approach to guide this technically challenging data integration task and to make knowledge discovery and hypotheses generation easier for plant and crop researchers. KnetMiner can digest large volumes of scientific literature and biological research to find and visualise links between the genetic and biological properties of complex traits and diseases. Here we report the main design principles behind KnetMiner and provide use cases for mining public datasets to identify unknown links between traits such grain colour and pre-harvest sprouting in Triticum aestivum, as well as, an evidence-based approach to identify candidate genes under an Arabidopsis thaliana petal size QTL. We have developed KnetMiner knowledge graphs and applications for a range of species including plants, crops and pathogens. KnetMiner is the first open-source gene discovery platform that can leverage genome-scale knowledge graphs, generate evidence-based biological networks and be deployed for any species with a sequenced genome. KnetMiner is available at http://knetminer.org.


title: A rapid systematic review and case study on test, contact tracing, testing, and isolation policies for Covid-19 prevention and control

text: Objectives To conduct a rapid review on the efficacy and policy of contact tracing, testing, and isolation (TTI) in Covid-19 prevention and control, including a case study for their delivery. Method Research articles and reviews on the use of contact tracing, testing, self-isolation and quarantine for Covid-19 management published in English within 1 year (2019 to 28th May, 2020) were eligible to the review. We searched MEDLINE (PubMed), Cochrane Library, SCOPUS and JSTOR with search terms included "contact tracing" or "testing" or "self-isolation" or "quarantine" in the title in combination with "Covid-19" or "COVID-19" or "coronavirus" in the title or abstract. Studies not associated with TTI or Covid-19 or being solely commentary were excluded. A narrative synthesis with a tabulation system was used to analyse studies for their diverse research designs, methods, and implications. Information for the case study was obtained from the Centers for Disease Control Taiwan. Results Among the 160 initial publications, 30 eligible studies are included in the review. Included studies applied various designs: experiments, clinical studies, Government Documents, systematic reviews, observational studies, surveys, practice guidelines, technical reports. A case study on TTI delivery is summarised based on policy and procedures in Taiwan. Conclusions The information included in the review may inform the TTI program in the UK.


Instantaneous contact tracing


title: Going by the Numbers : Learning and Modeling COVID-19 Disease Dynamics

text: The COrona VIrus Disease (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) has resulted in a challenging number of infections and deaths worldwide. In order to combat the pandemic, several countries worldwide enforced mitigation measures in the forms of lockdowns, social distancing and disinfection measures. In an effort to understand the dynamics of this disease, we propose a Long Short Term Memory (LSTM) based model. We train our model on over three months of cumulative COVID-19 cases and deaths. Our model can be adjusted based on the parameters in order to provide predictions as needed. We provide results at both the country and county levels. We also perform a quantitative comparison of mitigation measures in various counties in the United States based on the rate of difference of a short and long window parameter of the proposed LSTM model. The analyses provided by our model can provide valuable insights based on the trends in the rate of infections and deaths. This can also be of help for countries and counties deciding on mitigation and reopening strategies. We believe that the results obtained from the proposed method will contribute to societal benefits for a current global concern.


title: Efficacy of Chloroquine or Hydroxychloroquine in COVID-19 Patients: A Systematic Review and Meta-Analysis

text: Background The antimalarial agents, chloroquine (CQ) and hydroxychloroquine (HCQ) show promising SARS-CoV-2 anti-viral activity in vitro; however, clinical studies have reported conflicting results. We sought to systematically evaluate the effect of CQ and HCQ with or without azithromycin (AZ) on outcomes of COVID-19 patients. Methods We performed a systematic review and meta-analysis of studies published through July 7, 2020. We searched Medline, Embase, EBM Reviews, Scopus, Web of Science, preprints and grey literature. We included studies that assessed COVID-19 patients treated with CQ or HCQ, with or without AZ. We pooled only adjusted effect estimates of mortality using a random effect model and estimated between studies heterogeneity using I2 statistic. We summarized the effect of CQ or HCQ on viral clearance and ICU admission/ mechanical ventilation. Results Out of 1463 citations screened for eligibility, five RCTs and 14 cohort studies were included (20,263 patients, all hospitalized but with a variable disease severity spectrum). Thirteen studies (1 RCT and 12 cohorts) with 19,573 patients examined the effect of HCQ on short term mortality. The pooled adjusted OR was 1.05 (95% CI 0.96-1.15, I2=0 %, p=0.647). Six cohort studies examined the effect of HCQ and AZ combination among 3430 patients. After excluding a study that examined only patients with cancers, the pooled adjusted OR was (1.15, 95% CI 0.99-1.34, I2=0.0%). Two cohort studies and three RCTs found no significant effect of HCQ on viral clearance. One RCT with 48 patients demonstrated improved viral clearance in patients treated with CQ and HCQ. Three cohort studies found that HCQ with or without AZ had no significant effect on mechanical ventilation/ ICU admission. Conclusion Moderate certainty evidence suggests that HCQ, with or without AZ, lacks efficacy in reducing short-term mortality in patients hospitalized with COVID-19. Our findings are consistent with the recommendations from medical societies that HCQ should only be used to treat COVID-19 patients in the context of clinical trials. Trials of HCQ as pre-exposure prophylaxis are ongoing.


title: Ataxia as a presenting manifestation of COVID -19: Report of a single case

text: Even though various neurological presentations of COVID-19 have surfaced up, ataxia as a presenting feature has rarely been reported so far. We hereby describe a confirmed case of SARS-CoV-2 infection which not only presented with ataxia but also had delayed onset of typical respiratory features. This case represents an atypical manifestation of COVID-19.


title: Cellular exocytosis gene (EXOC6/6B): a potential molecular link for the susceptibility and mortality of COVID-19 in diabetic patients

text: Diabetes is one of the most critical comorbidities linked to an increased risk of severe complications in the current coronavirus disease 2019 (COVID-19) pandemic. A better molecular understanding of COVID-19 in people with type diabetes mellitus (T2D) is mandatory, especially in countries with a high rate of T2D, such as the United Arab Emirates (UAE). Identification of the cellular and molecular mechanisms that make T2D patients prone to aggressive course of the disease can help in the discovery of novel biomarkers and therapeutic targets to improve our response to the disease pandemic. Herein, we employed a system genetics approach to explore potential genomic, transcriptomic alterations in genes specific to lung and pancreas tissues, affected by SARS-CoV-2 infection, and study their association with susceptibility to T2D in Emirati patients. Our results identified the Exocyst complex component, 6 (EXOC6/6B) gene (a component for docks insulin granules to the plasma membrane) with documented INDEL in 3 of 4 whole genome sequenced Emirati diabetic patients. Publically available transcriptomic data showed that lung infected with SARS-CoV-2 showed significantly lower expression of EXOC6/6B compared to healthy lungs. In conclusion, our data suggest that EXOC6/6B might be an important molecular link between dysfunctional pancreatic islets and ciliated lung epithelium that makes diabetic patients more susceptible to severe SARS-COV-2 complication.


title: Lessons from mainland China's epidemic experience about the growth rules of infected and recovered cases of COVID-19 worldwide

text: The novel coronavirus disease (COVID-19) that emerged at the end of 2019 has been controlled in mainland China so far, while it is still spreading globally. When the pandemic will end is a question of great concern. A logistic model depicting the growth rules of infected and recovered cases in mainland China may shed some light on this question. We extended this model to 31 countries outside China experiencing serious COVID-2019 outbreaks. The model well explained the data in our study (R2 >0.95). For infected cases, the semi-saturation period (SSP) ranges from 63 to 170 days (March 3 to June 18). The logistic growth rate of infected cases is positively correlated with that of recovered cases, and the same holds for the SSP. According to the linear connection between the growth rules for infected and recovered cases identified from the Chinese data, we predicted that the SSP of the recovered cases outside China ranges from 82 to 196 days (March 22 to July 8). More importantly, we found a strong positive correlation between the SSP of infected cases and the timing of the government's response, providing strong evidence for the effectiveness of rapid epidemic control measures in various countries.


title: RNA-Dependent RNA Polymerase From SARS-CoV-2. Mechanism Of Reaction And Inhibition By Remdesivir

text: We combine sequence analysis, molecular dynamics and hybrid quantum mechanics/molecular mechanics simulations to obtain the first description of the mechanism of reaction of SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and of the inhibition of the enzyme by Remdesivir. Despite its evolutionary youth, the enzyme is highly optimized to have good fidelity in nucleotide incorporation and a good catalytic efficiency. Our simulations strongly suggest that Remdesivir triphosphate (the active form of drug) is incorporated into the nascent RNA replacing ATP, leading to a duplex RNA which is structurally very similar to an unmodified one. We did not detect any reason to explain the inhibitory activity of Remdesivir at the active site. Displacement of the nascent Remdesivir-containing RNA duplex along the exit channel of the enzyme can occur without evident steric clashes which would justify delayed inhibition. However, after the incorporation of three more nucleotides we found a hydrated Serine which is placed in a perfect arrangement to react through a Pinner’s reaction with the nitrile group of Remdesivir. Kinetic barriers for crosslinking and polymerization are similar suggesting a competition between polymerization and inhibition. Analysis of SARS-CoV-2 mutational landscape and structural analysis of polymerases across different species support the proposed mechanism and suggest that virus has not explored yet resistance to Remdesivir inhibition.


title: “Monoclonal-type” plastic antibodies for SARS-CoV-2 based on Molecularly Imprinted Polymers

text: Our idea is focused on the development of “monoclonal-type” plastic antibodies based on Molecularly Imprinted Polymers (MIPs) able to selectively bind a portion of the novel coronavirus SARS-CoV-2 spike protein to block its function and, thus, the infection process. Molecular Imprinting, indeed, represents a very promising and attractive technology for the synthesis of MIPs characterized by specific recognition abilities for a target molecule. Given these characteristics, MIPs can be considered tailor-made synthetic antibodies obtained by a templating process. In the present study, the developed imprinted polymeric nanoparticles were characterized in terms of particles size and distribution by Dynamic Light Scattering (DLS) and the imprinting effect and selectivity were investigated by performing binding experiments using the receptor-binding domain (RBD) of the novel coronavirus and the RBD of SARS-CoV spike protein, respectively. Finally, the hemocompatibility of the prepared MIP-based plastic antibodies was also evaluated.


title: Epidemiological and Clinical Features of SARS-CoV-2: A Retrospective Study from East Karachi, Pakistan

text: Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to almost every country on the globe, and each country is reporting the symptomatic presentation of their patients to give better insight into the various clinical presentations of SARS-CoV-2 However, the epidemiological literature from Pakistan is scanty Methods We retrospectively analyzed data from 412 patients who were residents of East Karachi and tested positive for SARS-CoV-2 between February 26 to April 24, 2020 Patients' demographics, symptoms, travel and contact history, and outcomes were recorded All statistical analysis was performed using the Statistical Package for the Social Sciences (SPSS) version 22 (IBM SPSS Statistics for Windows, IBM Corp, Armonk, NY) Results Most of the patients were male (64 6%), the majority (43 3%) belonging to the 21- to 40-year age group Most of the patients (65 5%) were residents of Gulshan Iqbal A total of 15 8% of the patients were admitted to the hospital, and 3 9% of patients expired The three most common presenting symptoms were fever (74 8%), cough (60 4%), and flu (35 5%) The majority of patients (89 3%) gave a history of contact with SARS-CoV-2 patients Conclusion The number of SARS-CoV-2 cases is rapidly increasing in Karachi, Pakistan There is a need to educate the population about the most common sign and symptoms of the virus so that individuals can identify these symptoms and get themselves tested The concerned authorities should devise an adequate and effective plan to flatten the infectivity curve


title: Biocompatibility of Subcutaneously Implanted Plant-Derived Cellulose Biomaterials

text: There is intense interest in developing novel biomaterials which support the invasion and proliferation of living cells for potential applications in tissue engineering and regenerative medicine. Decellularization of existing tissues have formed the basis of one major approach to producing 3D scaffolds for such purposes. In this study, we utilize the native hypanthium tissue of apples and a simple preparation methodology to create implantable cellulose scaffolds. To examine biocompatibility, scaffolds were subcutaneously implanted in wild-type, immunocompetent mice (males and females; 6-9 weeks old). Following the implantation, the scaffolds were resected at 1, 4 and 8 weeks and processed for histological analysis (H&E, Masson’s Trichrome, anti-CD31 and anti-CD45 antibodies). Histological analysis revealed a characteristic foreign body response to the scaffold 1 week post-implantation. However, the immune response was observed to gradually disappear by 8 weeks post-implantation. By 8 weeks, there was no immune response in the surrounding dermis tissue and active fibroblast migration within the cellulose scaffold was observed. This was concomitant with the deposition of a new collagen extracellular matrix. Furthermore, active blood vessel formation within the scaffold was observed throughout the period of study indicating the pro-angiogenic properties of the native scaffolds. Finally, while the scaffolds retain much of their original shape they do undergo a slow deformation over the 8-week length of the study. Taken together, our results demonstrate that native cellulose scaffolds are biocompatible and exhibit promising potential as a surgical biomaterial.


title: Viability of intertwined supply networks: extending the supply chain resilience angles towards survivability. A position paper motivated by COVID-19 outbreak

text: An intertwined supply network (ISN) is an entirety of interconnected supply chains (SC) which, in their integrity secure the provision of society and markets with goods and services. The ISNs are open systems with structural dynamics since the firms may exhibit multiple behaviours by changing the buyer-supplier roles in interconnected or even competing SCs. From the positions of resilience, the ISNs as a whole provide services to society (e.g. food service, mobility service or communication service) which are required to ensure a long-term survival. The analysis of survivability at the level of ISN requires a consideration at a large scale as resilience of individual SCs. The recent example of coronavirus COVID-19 outbreak clearly shows the necessity of this new perspective. Our study introduces a new angle in SC resilience research when a resistance to extraordinary disruptions needs to be considered at the scale of viability. We elaborate on the integrity of the ISN and viability. The contribution of our position study lies in a conceptualisation of a novel decision-making environment of ISN viability. We illustrate the viability formation through a dynamic game-theoretic modelling of a biological system that resembles the ISN. We discuss some future research areas.


Using Machine Learning to assess Covid-19 risks


title: No evidence that androgen regulation of pulmonary TMPRSS2 explains sex-discordant COVID-19 outcomes

text: The recent emergence of SARS-CoV-2 and the subsequent COVID-19 pandemic have posed a public health crisis. Higher morbidity and mortality of men with COVID-19 may be explained by androgen-driven mechanisms. One such proposed mechanism is androgen regulation of pulmonary TMPRSS2, the host co-receptor for SARS-CoV-2. We find no evidence for increased TMPRSS2 mRNA expression in the lungs of males compared to females in humans or mice. Furthermore, in male mice, treatment with the androgen receptor antagonist enzalutamide does not decrease pulmonary TMPRSS2 expression. Nevertheless, regardless of sex, smoking significantly increases the expression of TMPRSS2, which reverts back to never-smoker levels in former smokers. Finally, we show that in mouse models, despite equivalent AR transcript levels, males express markedly higher amounts of AR protein. If a similar sex-specific regulation of AR protein occurs in human lung, androgens could play important roles in clinical outcome of COVID-19 through mechanisms other than TMPRSS2 regulation.


title: Psychology in the prevention and management of covid-19. Contributions from the initial evidence/ La psicología en la prevención y manejo del covid-19. Aportes desde la evidencia inicial

text: In December 2019, highly lethal cases of pneumonia were reported in Wuhan, Hubei Province, China (COVID-19). This disease has spread rapidly around the world with thousands of confirmed cases and deaths, becoming a pandemic and challenging public health systems. There is no vaccine or scientifically proven treatment yet, but the exact behaviours that can prevent transmission and spread have been identified. This article systematizes initial available information on psychology and COVID-19. It is discussed that much of the problem of the disease can be avoided by changing people’s behaviors and that psychology can help explain, prevent and intervene to solve it. Psychology has scientific evidence available that explains all these phenomena, evidence that should be highlighted by the same actors in the disciplines available to other areas of knowledge and especially for decision makers.


docid: llqpfhwg

title: Antibody responses to SARS-CoV-2 in patients of novel coronavirus disease 2019

text: Summary Background The novel coronavirus SARS-CoV-2 is a newly emerging virus. The antibody response in infected patient remains largely unknown, and the clinical values of antibody testing have not been fully demonstrated. Methods A total of 173 patients with confirmed SARS-CoV-2 infection were enrolled. Their serial plasma samples (n = 535) collected during the hospitalization period were tested for total antibodies (Ab), IgM and IgG against SARS-CoV-2 using immunoassays. The dynamics of antibodies with the progress and severity of disease was analyzed. Findings Among 173 patients, the seroconversion rate for Ab, IgM and IgG was 93.1% (161/173), 82.7% (143/173) and 64.7% (112/173), respectively. Twelve patients who had not seroconverted were those only blood samples at the early stage of illness were collected. The seroconversion sequentially appeared for Ab, IgM and then IgG, with a median time of 11, 12 and 14 days, respectively. The presence of antibodies was < 40% among patients in the first 7 days of illness, and then rapidly increased to 100.0%, 94.3% and 79.8% for Ab, IgM and IgG respectively since day 15 after onset. In contrast, the positive rate of RNA decreased from 66.7% (58/87) in samples collected before day 7 to 45.5% (25/55) during days 15 to 39. Combining RNA and antibody detections significantly improved the sensitivity of pathogenic diagnosis for COVID-19 patients (p < 0.001), even in early phase of 1-week since onset (p = 0.007). Moreover, a higher titer of Ab was independently associated with a worse clinical classification (p = 0.006). Interpretation The antibody detection offers vital clinical information during the course of SARS-CoV-2 infection. The findings provide strong empirical support for the routine application of serological testing in the diagnosis and management of COVID-19 patients.