title: Viral Respiratory Pathogens Associated with Medically Attended Acute Respiratory Illnesses in Older Adults in Bulgaria

text: Acute respiratory infections (ARIs) are a major cause of morbidity and mortality among older adults This study aimed to determine the viral etiology of these infections in patients aged >= 65 years during two successive epidemic seasons in Bulgaria Nasal and throat specimens were collected from the enrolled patients during the 2015/2016 and 2016/2017 seasons The viral etiology was determined by individual Real Time PCR assays against 15 respiratory viruses Of the 160 adults examined, 74 (46 3%) were positive for at least one respiratory virus Co-infections with two and three viruses were found in 14 (18 9%) of the infected patients Influenza A(H3N2) (15 6%) and A(H1N1)pdm09 (13 1%) viruses were the predominant pathogens, followed by adenoviruses (5 6%);respiratory-syncytial virus (3 8%);metapneumovirus (3 1%);rhinoviruses (2 5%);coronaviruses - NL63 (2 5%), OC43 (1 9%), HKU1 (1 9%) and 229E (1 3%);influenza type B (1 9%);bocaviruses (1 3%) and parainfluenza viruses 1/2/3 (1 3%) At least one respiratory virus was identified in 50% and 32 3% of the patients with acute lower respiratory tract illnesses and neurological complications, respectively Respiratory viruses, especially influenza A viruses, are major pathogens of ARIs in persons aged >= 65 years Diagnostic testing for respiratory viruses using molecular methods can help in clinical decision making and may assist in measures to prevent health careassociated infections


title: Further Evidence of a Possible Correlation Between the Severity of Covid-19 and BCG Immunization

text: In this work we observe a number of cases supporting the possible correlation between the administration of BCG tuberculosis vaccine and the severity of Covid-19 effects in the population proposed in the earlier works [1]. Based on the early prelimi-nary analysis of the publicly available data we propose a number of arguments and observations providing further support for the correlation hypothesis and make an observation that the effectiveness of the protection effect of BCG im-munization, if confirmed, may depend to a significant extent on the age of admin-istration, with the early age inoculation more effective for the lasting protection..


title: Modeling the dynamics of COVID19 spread during and after social distancing

text: Non-pharmaceutical intervention measures, such as social distancing, have so far been the only means to slow the spread of COVID19. In the United States, strict social distancing has resulted in different types infection dynamics. In some states, such as New York, extensive infection spread was followed by a pronounced decline of infection levels. In other states, such as California, less infection spread occurred before strict social distancing, and a different pattern was observed. Instead of a pronounced infection decline, a long-lasting plateau is evident, characterized by similar daily new infection levels. While these plateau dynamics cannot be readily reproduced with standard SIR infection models, we show that network models, in which individuals and their social contacts are explicitly tracked, can reproduce the plateau if network connections are cut due to social distancing measures. The reason is that in networks characterized by a degree of 2D spatial structure, infection tends to spread quadratically with time, but as edges are randomly removed, the infection spreads along nearly one-dimensional infection "corridors", resulting in plateau dynamics. Interestingly, the plateau dynamics are predicted to eventually transition into an infection decline phase without any further increase in social distancing measures. Additionally, the models suggest that a potential second wave becomes significantly less pronounced if social distancing is only relaxed once the dynamics have transitioned to the decline phase. The network models analyzed here allow us to interpret and reconcile different infection dynamics during social distancing observed in various US states.


title: The scRNA-seq expression profiling of the receptor ACE2 and the cellular protease TMPRSS2 reveals human organs susceptible to COVID-19 infection

text: Background COVID-19 caused by SARA-CoV-2 is a disaster sweeping over 200 countries, and more than 2,150,000 people are suffering from the disease and 140,000 people died. ACE2 is a receptor protein of SARS- CoV-2, and TMPRSS2 promotes virus proliferation and transmission. Some patients developed multiple organ dysfunction syndromes other than lungs. Therefore, studying the viral susceptibility of other organs is important for a deeper understanding of viral pathogenesis. Methods The advantage of scRNA-seq data is the identification of cell types by clustering the gene expression of cells. ACE2 and TMPRSS2 are highly expressed in AT2 of lungs, we compared the ACE2 and TMPRSS2 expression levels of cell types from 31 organs, with AT2 of lungs to evaluate the risk of the viral infection using scRNA-seq data. Findings For the first time, we found the brain, gall bladder, and fallopian tube are vulnerable to COVID-19 infection. Besides, the nose, heart, small intestine, large intestine, esophagus, testis and kidney are also identified to be high-risk organs with high expression levels of ACE2 and TMPRSS2. Moreover, the susceptible organs are grouped into three risk levels based on the TMPRSS2 expression. As a result, the respiratory system, digestive system and reproductive system are at the top-risk level to COVID-19 infection. Interpretation This study provides evidence for COVID-19 infection in the human nervous system, digestive system, reproductive system, respiratory system, circulatory system and urinary system using scRNA-seq data, which helps for the clinical diagnosis and treatment of patients.


title: Tuberculosis diagnosis cascade in Blantyre, Malawi: a prospective cohort study

text: Background Tuberculosis (TB) control relies on early diagnosis and treatment. International guidelines recommend systematic TB screening at health facilities in high-burden settings, but implementation is challenging. To construct a TB diagnosis care cascade, we investigated screening guideline adherence and completion of TB testing steps in Blantyre, Malawi. Methods A prospective cohort recruited adult ([≥]18) outpatients attending Bangwe acute-care primary clinic between 21/5/2018 and 6/9/2018. Entry interviews recording TB symptoms and demographic characteristics were linked to exit interviews by biometrics. Care cascades were constructed to estimate the proportion of patients progressing through each step of the diagnostic pathway. Multivariable logistic regression was used to investigate factors associated with being asked to submit sputum. Results Of 5,442 clinic attendances 2,397 (44%) had exit interviews. In clinically indicated participants (n=330) 203 (61.5%) were asked about cough, 39 (11.8%) were asked for sputum, 27 (8.2%) gave sputum and 1 (0.3%) received same-day results. Significant associations with request for sputum were: any TB symptom (aOR:3.20, 95%CI:2.02-5.06), increasing age (aOR:1.02, 95%CI:1.01-1.04 per year) and for HIV-negative participants only, a history of previous TB (aOR:3.37, 95%CI:1.45-7.81). Numbers requiring sputum survey (20/day) outnumbered diagnostic capacity (8-12/day). Conclusion Patients were lost at every stage of the TB care cascade, with same day sputum submission achieved in only 8.2% if clinically indicated. Infection control strategies should be implemented, with reporting on early steps of the TB care cascade formalised. High-throughput interventions, such as digital CXR, that can optimise same-day TB screening are urgently needed to meet WHO End TB goals.


title: Diligent medical activities of a publicly designated medical institution for infectious diseases pave the way for overcoming COVID-19: A positive message to people working at the cutting edge

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), is highly infectious and has spread worldwide. An important factor compounding spread is the infection of medical staff with SARS-CoV-2, which threatens the collapse of the very institutions required to treat COVID-19. The possibility of virus transmission from patients with COVID-19 to medical staff is thus of primary concern. Asymptomatic COVID-19 carriage among hospital staff could also be conceivable to act as a potent source of ongoing transmission. Here we show that, surprisingly, none of the medical staff working at a hospital with COVID-19 patients had IgG antibodies for SARS-CoV-2, indicating that virus transmission from patients to medical staff did not occur in these medical workers. These results show that standard preventive measures against infectious diseases can prevent SARS-CoV-2 exposure in medical staff, and should greatly encourage medical practitioners at the front line of this pandemic.


title: A modified SEIR Model with Confinement and Lockdown of COVID-19 for Costa Rica

text: The fast moving post-modern society allows for individuals to move fast in and between different countries, making it a perfect situation for the spread of emerging diseases. COVID-19 emerged with properties of a highly contagious disease, that has spread rapidly around the world. SIR/SEIR models are generally used to explain the dynamics of epidemics, however Coronavirus has shown dynamics with constant non-pharmaceutical interventions, making it difficult to model with these simple models. We extend an SEIR model to include a confinement compartment (SEICR) and use this to explain data from COVID-19 epidemic in Costa Rica. Then we discuss possible second wave of infection by adding a time varying function in the model to simulate cyclic interventions.


title: Senators call for $2 billion in supplemental SAMHSA funding

text: As the fourth stimulus bill, the HEROES Act, awaits action by the Senate, 19 senators sent a letter last week to Senate and House leadership calling for increased investments in substance use disorder programs during the COVID-19 pandemic The letter, from Senators Tammy Baldwin (D-Wisconsin) and Jeanne Shaheen (D-New Hampshire), along with 17 other senators (all Democrats), calls for ?$2 billion in funding for the Substance Abuse and Mental Health Services Administration (SAMHSA) to administer supplemental grant allocations under the Substance Abuse Prevention and Treatment (SAPT) Block Grant program and the State Opioid Response (SOR) grant program ?


The Role of Hydroxychloroquine in Coronavirus Disease 2019. A Versatile Tool at the Service of Humanity


title: UV-C Tower for point-of-care decontamination of filtering facepiece respirators

text: Filtering facepiece respirators (FFR) are critical for protecting essential personnel and limiting the spread of disease. Due to the current COVID-19 pandemic, FFR supplies are dwindling in many health systems, necessitating re-use of potentially contaminated FFR. Multiple decontamination solutions have been developed to meet this pressing need, including systems designed for bulk decontamination of FFR using vaprous hydrogen peroxide or UV-C radiation. However, the large scale on which these devices operate may not be logistically practical for small or rural health care settings or for ad hoc use at points-of-care. Here, we present the Synchronous UV Decontamination System (SUDS), a novel device for rapidly deployable, point-of-care decontamination using UV-C germicidal irradiation. We designed a compact, easy-to-use device capable of delivering over 2 J/cm^2 of UV-C radiation in one minute. This short decontamination time should enable care-providers to incorporate decontamination of FFR into a normal donning and doffing routine following patient encounters.


title: A Semiempirical Dynamical Model to Forecast the Propagation of Epidemics: The Case of the Sars-Cov-2 in Spain

text: A semiempirical model, based in the logistic map, has been succesfully applied to forecast important quantities along the several phases of the outbreak of the covid-19 for different countries. This paper shows how the model was calibrated and applied to perform predictions of people needing to be hospitalized, needs of ventilators, or the number of deaths which would be produced. It is shown specifically the results obtained in the case of Spain, showing a prediction of diagnosed infected and deaths which will be observed after the ease of the total lockdown produced the 13th of March. Is also shown how this model can provide an insight of what the level of infection in the different regions of Spain is forecasted. The model predicts for Spain for the end of May more than 400,000 diagnosed infected cases, number which will be probably higher due to the change in the possibilities of performing massive number of tests to the general population. The number of forecasted deaths for that date is 46,000 +/- 15,000. The model also predicts the level of infection at the different Spanish regions, providing a counterintuitive result in the cases of Madrid and Catalonia as the result shows a higher the level of infection at Catalonia than the level at Madrid, according with this model. All of these results can be used to guide policy makers in order to optimize resources and to avoid future outbreaks of the covid-19.


title: Functional Immune Deficiency Syndrome via Intestinal Infection in COVID-19

text: Using a Systems Biology approach, we integrated genomic, transcriptomic, proteomic, and molecular structure information to provide a holistic understanding of the COVID-19 pandemic. The expression data analysis of the Renin Angiotensin System indicates mild nasal, oral or throat infections are likely and that the gastrointestinal tissues are a common primary target of SARS-CoV-2. Extreme symptoms in the lower respiratory system likely result from a secondary-infection possibly by a comorbidity-driven upregulation of ACE2 in the lung. The remarkable differences in expression of other RAS elements, the elimination of macrophages and the activation of cytokines in COVID-19 bronchoalveolar samples suggest that a functional immune deficiency is a critical outcome of COVID-19. We posit that using a non-respiratory system as a major pathway of infection is likely determining the unprecedented global spread of this coronavirus. One Sentence Summary A Systems Approach Indicates Non-respiratory Pathways of Infection as Key for the COVID-19 Pandemic


title: Lies, Gosh Darn Lies, and Not Enough Good Statistics: Why Epidemic Model Parameter Estimation Fails

text: An opportunity exists in exploring epidemic modeling as a novel way to determine physiological and demic parameters for genetic association studies on a population/environmental (quasi) epidemiological study level. First, the spread of SARS-COV-2 has produced population specific lineages; second, epidemic spread model parameters are tied directly to these physiological and demic rates (e. g. incubation time, recovery time, transmission rate); and third, these parameters may serve as novel phenotypes to associate with region-specific genetic mutations as well as demic characteristics (e. g. age structure, cultural observance of personal space, crowdedness). Therefore, we sought to understand whether the parameters of epidemic models could be determined from the trajectory of infections, recovery, and hospitalizations prior to peak, and also to evaluate the quality and comparability of data between jurisdictions reporting their statistics necessary for the analysis of model parameters across populations. We found that, analytically, the pre-peak growth of an epidemic is limited by a subset of the model variates, and that the rate limiting variables are dominated by the expanding eigenmode of their equations. The variates quickly converge to the ratio of eigenvector components of the positive growth rate, which determines the doubling time. There are 9 parameters and 4 independent components in the eigenmode, leaving 5 undetermined parameters. Those parameters can be strikingly population dependent, and can have significant impact on estimates of hospital loads downstream. Without a sound framework, measurements of infection rates and other parameters are highly corrupted by uneven testing rates to uneven counting and reporting of relevant values. From the standpoint of phenotype parameters, this means that structured experiments must be performed to estimate these parameters in order to perform genetic association studies, or to construct viable models that accurately predict critical quantities such as hospitalization loads.


Repurposing Surgical Wrap Textiles for Use as Protective Masks During Pandemic Response


title: Covid-19 and Intrinsic Capacity

text: The SARS-CoV-2 infection is particularly associated with negative outcomes (i.e., serious disease, death) in frail older people, independently of where they live. Furthermore, the period of pandemic (with its lockdowns, social distancing, fragmentation of care..) has significantly changed the environment in which older people live. It is likely that, when the pandemic will be over, an acceleration of the aging process will be observed for many persons, independently of whether they have been infected or not by the SARS-CoV-2. The World report on ageing and health, published by the World Health Organization, proposes the concept of intrinsic capacity (i.e., the composite of all the physical and mental capacities of the individual) as central for healthy ageing. The routine assessment of biological age through constructs such as intrinsic capacity might have allowed a better understanding of the functional trajectories and vulnerabilities of the individual, even during a catastrophic event as the one we are currently living. In the present article, we describe how COVID-19 has affected the persons’ intrinsic capacity, and how the wide adoption of the intrinsic capacity model may support the modernization of our systems and bring them closer to the individual.


title: Initial evidence of higher morbidity and mortality due to SARS-CoV-2 in regions with lower air quality

text: COVID-19 has spread in all continents in a span of just over three months, escalating into a pandemic that poses several humanitarian as well as scientific challenges. We here investigated the geographical expansion of the infection and correlate it with the annual indexes of air quality observed from the Sentinel-5 satellite orbiting around China, Italy and the U.S.A. Controlling for population size, we find more viral infections in those areas afflicted by Carbon Monoxide (CO) and Nitrogen Dioxide (NO2). Higher mortality was also correlated with poor air quality, namely with high PM2.5, CO and NO2 values. In Italy, the correspondence between poor air quality and SARS-CoV-2 appearance and induced mortality was the starkest. Similar to smoking, people living in polluted areas are more vulnerable to SARS-CoV-2 infections and induced mortality. This further suggests the detrimental impact climate change will have on the trajectory of future epidemics.


title: Evaluation of the awareness level of Healthcare workers toward NCOVID-2019 in Pakistan

text: Background Novel Coronavirus infection disease 2019 (NCOVID-19), caused by the corona virus, was first spotted in Wuhan, city of China, December 2019. The NCOVID-19 virus is spread among individuals through close communication in the form of droplets, not via airborne. Those individuals are at risk of infection who are in close contact with a NCOVID-19 patient or who take care of NCOVID-19 patients. Infection prevention and control measures are critical to prevent the possible spread of any infection in healthcare facilities. Therefore, healthcare workers should be aware of basic knowledge and all procedures concerning prevention and protection from NCOVID-19. Objective The objective of this study was to evaluate the awareness level of healthcare workers toward NCOVID-2019 in Pakistan. Material and Methods A questionnaire was generated according to WHO information that was circulated among the healthcare workers of different hospitals and medical institutes of Pakistan. Calculated sample size was 650. Conclusion Healthcare workers have insufficient knowledge of preventive measures and infection control. The authorities must take initiatives on urgent basis to increase the awareness among the healthcare workers and general public also so that the drastic circumstances can be avoided in the developing country like Pakistan.


title: Angiotensin‐converting enzyme‐2 (ACE2), SARS‐CoV‐2 and pathophysiology of coronavirus disease 2019 (COVID‐19)

text: Angiotensin‐converting enzyme‐2 (ACE2) has been established as the functional host receptor for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the virus responsible for the current devastating worldwide pandemic of coronavirus disease 2019 (COVID‐19). ACE2 is abundantly expressed in a variety of cells residing in many different human organs. In human physiology, ACE2 is a pivotal counter‐regulatory enzyme to ACE by the breakdown of angiotensin II, the central player in the renin‐angiotensin‐aldosterone system (RAAS) and the main substrate of ACE2. Many factors have been associated with both altered ACE2 expression and COVID‐19 severity and progression, including age, sex, ethnicity, medication and several co‐morbidities, such as cardiovascular disease and metabolic syndrome. Although ACE2 is widely distributed in various human tissues and many of its determinants have been well recognised, ACE2‐expressing organs do not equally participate in COVID‐19 pathophysiology, implying that other mechanisms are involved in orchestrating cellular infection resulting in tissue damage. Reports of pathologic findings in tissue specimens of COVID‐19 patients are rapidly emerging and confirm the established role of ACE2 expression and activity in disease pathogenesis. Identifying pathologic changes caused by SARS‐CoV‐2 infection is crucially important as it has major implications for understanding COVID‐19 pathophysiology and the development of evidence‐based treatment strategies. Currently, many interventional strategies are being explored in ongoing clinical trials, encompassing many drug classes and strategies, including antiviral drugs, biological response modifiers and RAAS inhibitors. Ultimately, prevention is key to combat COVID‐19 and appropriate measures are being taken accordingly, including development of effective vaccines. In this review, we describe the role of ACE2 in COVID‐19 pathophysiology, including factors influencing ACE2 expression and activity in relation to COVID‐19 severity. In addition, we discuss the relevant pathological changes resulting from SARS‐CoV‐2 infection. Finally, we highlight a selection of potential treatment modalities for COVID‐19. This article is protected by copyright. All rights reserved.


On Dynamical Analysis of the Data-DrivenSIR model (COVID-19 Outbreak in Indonesia)


Acute Small Bowel Pathology: Spectrum of Nonneoplastic Diseases on CT Updates on COVID-19 Infection During Pregnancy


title: Autophagy in T cells from aged donors is maintained by spermidine, and correlates with function and vaccine responses

text: Older adults are at high risk for infectious diseases such as the recent COVID-19 and vaccination seems to be the only long-term solution to the pandemic. While most vaccines are less efficacious in older adults, little is known about the molecular mechanisms that underpin this. Autophagy, a major degradation pathway and one of the few processes known to prevent aging, is critical for the maintenance of immune memory in mice. Here, we show induction of autophagy is specifically induced in human vaccine-induced antigen-specific T cells in vivo. Reduced IFNγ secretion by vaccine-induced T cells in older vaccinees correlates with low autophagy. We demonstrate in human cohorts that levels of the endogenous autophagy-inducing metabolite spermidine, fall with age and supplementing it in vitro recovers autophagy and T cell function. Finally, our data show that endogenous spermidine maintains autophagy via the translation factor eIF5A and transcription factor TFEB. With these findings we have uncovered novel targets and biomarkers for the development of anti-aging drugs for human T cells, providing evidence for the use of spermidine in improving vaccine immunogenicity in the aged human population.


title: Optimal timing for social distancing during an epidemic

text: Social distancing is an effective way to contain the spread of a contagious disease, particularly when facing a novel pathogen and no pharmacological interventions are available. In such cases, conventional wisdom suggests that social distancing measures should be introduced as soon as possible after the beginning of an outbreak to more effectively mitigate the spread of the disease. Using a simple epidemiological model we show that, however, there is in fact an optimal time to initiate a temporal social distancing intervention if the goal is to reduce the final epidemic size or flatten the epidemic curve. The optimal timing depends strongly on the effective reproduction number (R0) of the disease, such that as the R0 increases, the optimal time decreases non-linearly. Additionally, if pharmacological interventions (e.g., a vaccine) become available at some point during the epidemic, the sooner these interventions become available the sooner social distancing should be initiated to maximize its effectiveness. Although based on a simple model, we hope that these insights inspire further investigations within the context of more complex and data-driven epidemiological models, and can ultimately help decision makers to improve temporal social distancing policies to mitigate the spread of epidemics.


title: Enhanced Contact Investigations for Nine Early Travel-Related Cases of SARS-CoV-2 in the United States

text: Background Coronavirus disease 2019 (COVID-19), the respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and has since become pandemic. As part of initial response activities in the United States, enhanced contact investigations were conducted to enable early identification and isolation of additional cases and to learn more about risk factors for transmission. Methods Close contacts of nine early travel-related cases in the United States were identified. Close contacts meeting criteria for active monitoring were followed, and selected individuals were targeted for collection of additional exposure details and respiratory samples. Respiratory samples were tested for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (RT-PCR) at the Centers for Disease Control and Prevention. Results There were 404 close contacts who underwent active monitoring in the response jurisdictions; 338 had at least basic exposure data, of whom 159 had at least 1 set of respiratory samples collected and tested. Across all known close contacts under monitoring, two additional cases were identified; both secondary cases were in spouses of travel-associated case patients. The secondary attack rate among household members, all of whom had at least 1 respiratory sample tested, was 13% (95% CI: 4 - 38%). Conclusions The enhanced contact tracing investigations undertaken around nine early travel-related cases of COVID-19 in the United States identified two cases of secondary transmission, both spouses. Rapid detection and isolation of the travel-associated case patients, enabled by public awareness of COVID-19 among travelers from China, may have mitigated transmission risk among close contacts of these cases.


docid: slxvexar

title: Reaction to the COVID-19 Pandemic: The Influence of Meaning in Life, Life Satisfaction, and Assumptions on World Orderliness and Positivity

text: The goal of the research was to measure the impact of the meaning in life, life satisfaction, and the beliefs in orderliness and positivity of the social world on emotional and cognitive reactions to the COVID-19 pandemic. The 317 participants were recruited over four days (April 1st–4th) during the start of the dynamic increase of the pandemic in Poland. The study was performed via open-access forums on the internet. The analyses indicated that stronger basic hope and higher levels of meaning in life and life satisfaction correlate with lower state anxiety and lower COVID-19 stress. Mediation analyses suggested the following interpretation of the interdependencies: basic hope supports meaning in life and life satisfaction and the increase in the latter two factors results in lower anxiety and COVID-19 stress. The results suggest that these three global assumptions and feelings may serve as buffers against anxiety as well as nonproductive thinking and decision making in the face of an unpredictable threat.


title: COVID-19: A New Virus as a Potential Rapidly Spreading in the Worldwide

text: Covid-19 is a novel virus with high affinity to spread in the community In December 2019, it was first identified in Wuhan, China The symptoms are non-specific, so fever, cough, dyspnea, are prominent features Respiratory failure and mortality have also been reported The most common lung CT scan findings are bilateral ground glass opacities


title: Cells and gene expression programs in the adult human heart

text: Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and strategies to improve therapeutic opportunities require deeper understanding of the molecular processes of the normal heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavor. Here, using large-scale single cell and nuclei transcriptomic profiling together with state-of-the-art analytical techniques, we characterise the adult human heart cellular landscape covering six anatomical cardiac regions (left and right atria and ventricles, apex and interventricular septum). Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, revealing distinct subsets in the atria and ventricles indicative of diverse developmental origins and specialized properties. Further we define the complexity of the cardiac vascular network which includes clusters of arterial, capillary, venous, lymphatic endothelial cells and an atrial-enriched population. By comparing cardiac cells to skeletal muscle and kidney, we identify cardiac tissue resident macrophage subsets with transcriptional signatures indicative of both inflammatory and reparative phenotypes. Further, inference of cell-cell interactions highlight a macrophage-fibroblast-cardiomyocyte network that differs between atria and ventricles, and compared to skeletal muscle. We expect this reference human cardiac cell atlas to advance mechanistic studies of heart homeostasis and disease.


title: Modeling Tempo of COVID-19 Pandemic in India and Significance of Lockdown

text: A very special type of pneumonic disease that generated the COVID-19 pandemic was first identified in Wuhan, China in December 2019 and is spreading all over the world. The ongoing outbreak presents a challenge for data scientists to model COVID-19, when the epidemiological characteristics of the COVID-19 are yet to be fully explained. The uncertainty around the COVID-19 with no vaccine and effective medicine available until today create additional pressure on the epidemiologists and policy makers. In such a crucial situation, it is very important to predict infected cases to support prevention of the disease and aid in the preparation of healthcare service. In this paper, we have tried to understand the spreading capability of COVID-19 in India taking into account of the lockdown period. The numbers of confirmed cases are increased in India and states in the past few weeks. A differential equation based simple model has been used to understand the pattern of COVID-19 in India and some states. Our findings suggest that the physical distancing and lockdown strategies implemented in India are successfully reducing the spread and that the tempo of pandemic growth has slowed in recent days.


title: Feature Driven and Point Process Approaches for Popularity Prediction

text: Predicting popularity, or the total volume of information outbreaks, is an important subproblem for understanding collective behavior in networks. Each of the two main types of recent approaches to the problem, feature-driven and generative models, have desired qualities and clear limitations. This paper bridges the gap between these solutions with a new hybrid approach and a new performance benchmark. We model each social cascade with a marked Hawkes self-exciting point process, and estimate the content virality, memory decay, and user influence. We then learn a predictive layer for popularity prediction using a collection of cascade history. To our surprise, Hawkes process with a predictive overlay outperform recent feature-driven and generative approaches on existing tweet data [43] and a new public benchmark on news tweets. We also found that a basic set of user features and event time summary statistics performs competitively in both classification and regression tasks, and that adding point process information to the feature set further improves predictions. From these observations, we argue that future work on popularity prediction should compare across feature-driven and generative modeling approaches in both classification and regression tasks.


title: Identification of neutralizing human monoclonal antibodies from Italian Covid-19 convalescent patients

text: In the absence of approved drugs or vaccines, there is a pressing need to develop tools for therapy and prevention of Covid-19. Human monoclonal antibodies have very good probability of being safe and effective tools for therapy and prevention of SARS-CoV-2 infection and disease. Here we describe the screening of PBMCs from seven people who survived Covid-19 infection to isolate human monoclonal antibodies against SARS-CoV-2. Over 1,100 memory B cells were single-cell sorted using the stabilized prefusion form of the spike protein and incubated for two weeks to allow natural production of antibodies. Supernatants from each cell were tested by ELISA for spike protein binding, and positive antibodies were further tested for neutralization of spike binding to receptor(s) on Vero E6 cells and for virus neutralization in vitro. From the 1,167 memory B specific for SARS-CoV-2, we recovered 318 B lymphocytes expressing human monoclonals recognizing the spike protein and 74 of these were able to inhibit the binding of the spike protein to the receptor. Finally, 17 mAbs were able to neutralize the virus when assessed for neutralization in vitro. Lead candidates to progress into the drug development pipeline will be selected from the panel of neutralizing antibodies identified with the procedure described in this study. One Sentence Summary Neutralizing human monoclonal antibodies isolated from Covid-19 convalescent patients for therapeutic and prophylactic interventions.


title: COVID-19 as an Emerging Risk: How to Bridge the Gap between Science and Policy

text: In this paper, I considered the novel coronavirus pandemic as general as possible from the aspects of emerging risks and the relationship between science and policy For the former, it was proposed to institutionalize mechanisms such as national risk assessments carried out in other countries, and for the latter, to visualize the process from scientific facts to the determination of risk management measures In addition, responding to the novel coronavirus requires the involvement of experts not only from a medical point of view, but also from a behavioral point of view


title: The Coming Coronavirus Crisis: What Can We Learn?

text: The coronavirus pandemic is bringing with it the prospect of severe financial and economic crises. The article investigates its economic consequences in terms of financial instability, economic recession, lower incomes and policy challenges at the national and European levels. What are some of the lessons that can be learned? This article argues that health is a global public good. Public health and welfare systems are crucial alternatives to the market and universal public health is a key element of an egalitarian policy.


title: The impact of the COVID-19 pandemic on quality of life, physical and psychosocial wellbeing in breast cancer patients and survivors - A prospective, multicenter cohort study

text: Purpose: The COVID-19 pandemic and the resulting social distancing and lockdown measures are having a substantial impact on daily life and medical management of people with breast cancer. We evaluated to what extent these changes have affected quality of life and physical, and psychosocial wellbeing of people (being) treated for breast cancer. Methods: This study was conducted within the prospective Utrecht cohort for Multiple BREast cancer intervention studies and Long-term evaluation (UMBRELLA). Shortly after the implementation of COVID-19 measures, extra questionnaires were sent to 1595 cohort participants, including standard UMBRELLA quality of life (EORTC) questionnaires. Patient-reported outcomes (PROs) were compared to the most recent PROs collected within UMBRELLA before COVID-19. The impact of COVID-19 on PROs was evaluated using mixed models analysis. Results: In total, 1051 patients (66%) completed the questionnaires. One third (n = 327, 31%) reported a higher threshold to contact their general practitioner due to COVID-19. A significant deterioration in emotional functioning was observed (82.6 to 77.9, p < 0.001) and 505 (48%, 95% CI 45-51) patients reported moderate to severe loneliness. Small significant improvements were observed in QoL, physical-, social- and role functioning scores. In the subgroup of 51 patients under active treatment, there was a strong deterioration in social functioning (69.8 to 5.0, p = 0.03). Conclusion: Due to COVID-19, patients (being) treated for breast cancer are less likely to contact physicians, and experience a deterioration in emotional functioning. Patients undergoing active treatment report a strong drop in social functioning. One in two patients reports (severe) loneliness. Online applications facilitating peer contact and e-mental health interventions could support mental health and social interaction times of total lockdown or social distancing.


title: Non-pharmaceutical behavioural measures for droplet-borne biological hazards prevention: Health-EDRM for COVID-19 (SARS-CoV-2) pandemic

text: Introduction: Non-pharmaceutical interventions to facilitate response to the COVID-19 pandemic, a disease caused by novel coronavirus SARS-CoV-2, are urgently needed. Using the WHO health emergency and disaster risk management (health-EDRM) framework, behavioural measures for droplet-borne communicable disease, with their enabling and limiting factors at various implementation levels were evaluated. Sources of data: Keyword search was conducted in PubMed, Google Scholar, Embase, Medline, Science Direct, WHO and CDC online publication database. Using OCEBM as review criteria, 105 English-language articles, with ten bottom-up, non-pharmaceutical prevention measures, published between January 2000 and May 2020 were identified and examined. Areas of Agreement: Evidence-guided behavioural measures against COVID-19 transmission for global at-risk communities are identified. Area of Concern: Strong evidence-based systematic behavioural studies for COVID-19 prevention are lacking. Growing points: Very limited research publications are available for non-pharmaceutical interventions to facilitate pandemic response. Areas timely for research: Research with strong implementation feasibility that targets resource-poor settings with low baseline Health-EDRM capacity is urgently need.


title: The values of coagulation function in COVID-19 patients

text: Objective: To investigate the blood coagulation function in COVID-19 patients, and the correlation between coagulopathy and disease severity. Methods: We retrospectively collected 147 clinically diagnosed COVID-19 patients at Wuhan Leishenshan Hospital of Hubei, China. We analyzed the coagulation function in COVID-19 patients through the data including thrombin-antithrombin complex (TAT), 2-plasmininhibitor-plasmin Complex (PIC), thrombomodulin (TM), t-PA/PAI-1 Complex (t-PAIC), prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), D-Dimer (DD), and platelet (PLT). Result: The levels of TAT, PIC, TM, t-PAIC, PT, INR, FIB, and DD in COVID-19 patients were higher than health controls (p<0.05), and also higher in the patients with thrombotic disease than without thrombotic disease (p<0.05). What's more, the patients with thrombotic disease had a higher case-fatality (p<0.05). TAT, PIC, TM, t-PAIC, PT, INR, APTT, FIB, DD, and PLT were also found correlated with disease severity. Meanwhile, we found that there were significant difference in TAT, TM, t-PAIC, PT, INR, APTT, DD, and PLT in the death and survival group. Further using univariate and multivariate logistic regression analysis also found that t-PAIC and DD were independent risk factors for death in patients and are excellent predicting the mortality risk of COVID-19. Conclusion: The coagulation systems in COVID-19 patients are inordinate, and dynamic monitoring of them, might be a key in the control of COVID-19 death.


title: Quantification of SARS-CoV-2 viral copy number in saliva mouthwash samples using digital droplet PCR

text: Saliva samples were collected through a simple mouth wash procedure and viral load quantified using a technology called digital droplet PCR. Data suggest ddPCR is allows for precise quantification of viral load in clinical samples infected with SARS-CoV-2.


title: Structure of RNA-dependent RNA polymerase from 2019-nCoV, a major antiviral drug target

text: A novel coronavirus (2019-nCoV) outbreak has caused a global pandemic resulting in tens of thousands of infections and thousands of deaths worldwide. The RNA-dependent RNA polymerase (RdRp, also named nsp12), which catalyzes the synthesis of viral RNA, is a key component of coronaviral replication/transcription machinery and appears to be a primary target for the antiviral drug, remdesivir. Here we report the cryo-EM structure of 2019-nCoV full-length nsp12 in complex with cofactors nsp7 and nsp8 at a resolution of 2.9-Å. Additional to the conserved architecture of the polymerase core of the viral polymerase family and a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain featured in coronaviral RdRp, nsp12 possesses a newly identified β-hairpin domain at its N-terminal. Key residues for viral replication and transcription are observed. A comparative analysis to show how remdesivir binds to this polymerase is also provided. This structure provides insight into the central component of coronaviral replication/transcription machinery and sheds light on the design of new antiviral therapeutics targeting viral RdRp. One Sentence Summary Structure of 2019-nCov RNA polymerase.


title: Molecular Docking Analysis Of Some Phytochemicals On Two SARS-CoV-2 Targets: Potential Lead Compounds Against Two Target Sites of SARS-CoV-2 Obtained from Plants

text: COV spike (S) glycoprotein and Mpro are two key targets that have been identified for vaccines and drug development against the COVID-19 disease. Virtual screening of some compounds of plants origin that have shown antiviral activities were carried out on the two targets, 6lu7 and 6vsb by docking with the PyRx software. The binding affinities were compared with other compounds and drugs already identified as potential ligands for 6lu7 and 6vsb as well as Chloroquine and hydroxychloroquine. The docked compounds with best binding affinities were also filtered for drug likeness using the SwissADME and PROTOX platforms on the basis of Physicochemical properties and toxicity respectively. The docking results revealed that scopodulcic acid and dammarenolic acid had the best binding affinity on the s-glycoprotein and Mpro protein targets respectively. Silybinin also demonstrated a good binding affinity to both protein targets making it a potential candidate for further evaluation as repurposed candidate for SARS COV2 with likelihood of having a multitarget activity.


title: Association between comorbidities and the risk of death in patients with COVID-19: sex-specific differences

text: Background: The coronavirus disease 2019 (Covid-19) spreads rapidly around the world. Objective: To evaluate the association between comorbidities and the risk of death in patients with COVID-19, and to further explore potential sex-specific differences. Methods: We analyzed the data from 18,465 laboratory-confirmed cases that completed an epidemiological investigation in Hubei Province as of February 27, 2020. Information on death was obtained from the Infectious Disease Information System. The Cox proportional hazards model was used to estimate the association between comorbidities and the risk of death in patients with COVID-19. Results: The median age for COVID-19 patients was 50.5 years. 8828(47.81%) patients were females. Severe cases accounted for 20.11% of the study population. As of March 7, 2020, a total of 919 cases deceased from COVID-19 for a fatality rate of 4.98%. Hypertension (13.87%), diabetes (5.53%), and cardiovascular and cerebrovascular diseases CBVDs (4.45%) were the most prevalent comorbidities, and 27.37% of patients with COVID-19 reported having at least one comorbidity. After adjustment for age, gender, address, and clinical severity, patients with hypertension (HR 1.55, 95%CI 1.35-1.78), diabetes (HR 1.35, 95%CI 1.13-1.62), CBVDs (HR 1.70, 95%CI 1.43-2.02), chronic kidney diseases (HR 2.09, 95%CI 1.47-2.98), and at least two comorbidities (HR 1.84, 95%CI 1.55-2.18) had significant increased risks of death. And the association between diabetes and the risk of death from COVID-19 was prominent in women (HR 1.69, 95%CI 1.27-2.25) than in men (HR 1.16, 95%CI 0.91-1.46) (P for interaction = 0.036). Conclusion: Among laboratory-confirmed cases of COVID-19 in Hubei province, China, patients with hypertension, diabetes, CBVDs, chronic kidney diseases were significantly associated with increased risk of death. The association between diabetes and the risk of death tended to be stronger in women than in men. Clinicians should increase their awareness of the increased risk of death in COVID-19 patients with comorbidities.


title: Deep Learning-Based Intelligent Defect Detection of Cutting Wheels with Industrial Images in Manufacturing

text: Abstract The cutting wheel is an important tool in the television liquid crystal display (LCD) panel manufacturing process. The degradation of the cutting wheel significantly affects the LCD panel quality. Currently, there is few effective approaches that can detect the degradation of the cutting wheel at the working station for health monitoring purpose, due to the small size of the component and the complex manufacturing operation. That leads to high economic costs in the production lines in the real industries. In order to address this issue, this paper presents a deep convolutional neural network-based method for defect detection of the cutting wheels using the industrial images. An end-to-end health monitoring system is built based on machine vision, which directly takes the raw images as inputs, and outputs the detection results. That facilitates the industrial applications since little prior knowledge on image processing and fault detection is required. The experiments on a real-world cutting wheel degradation dataset are carried out for validation. High fault diagnosis testing accuracies are obtained, that indicates the proposed method offers an effective and promising approach for the cutting wheel health monitoring problem.


title: Assessing Differential Impacts of COVID-19 on Black Communities

text: Purpose Given incomplete data reporting by race, we used data on COVID-19 cases and deaths in US counties to describe racial disparities in COVID-19 disease and death and associated determinants. Methods Using publicly available data (accessed April 13, 2020), predictors of COVID-19 cases and deaths were compared between disproportionately (>13%) black and all other (<13% black) counties. Rate ratios were calculated and population attributable fractions (PAF) were estimated using COVID-19 cases and deaths via zero-inflated negative binomial regression model. National maps with county-level data and an interactive scatterplot of COVID-19 cases were generated. Results Nearly ninety-seven percent of disproportionately black counties (656/677) reported a case and 49% (330/677) reported a death versus 81% (1987/2,465) and 28% (684/ 2465), respectively, for all other counties. Counties with higher proportions of black people have higher prevalence of comorbidities and greater air pollution. Counties with higher proportions of black residents had more COVID-19 diagnoses (RR 1.24, 95% CI 1.17-1.33) and deaths (RR 1.18, 95% CI 1.00-1.40), after adjusting for county-level characteristics such as age, poverty, comorbidities, and epidemic duration. COVID-19 deaths were higher in disproportionally black rural and small metro counties. The PAF of COVID-19 diagnosis due to lack of health insurance was 3.3% for counties with <13% black residents and 4.2% for counties with >13% black residents. Conclusions Nearly twenty-two percent of US counties are disproportionately black and they accounted for 52% of COVID-19 diagnoses and 58% of COVID-19 deaths nationally. County-level comparisons can both inform COVID-19 responses and identify epidemic hot spots. Social conditions, structural racism, and other factors elevate risk for COVID-19 diagnoses and deaths in black communities.


COVID-19 and Underlying Cerebrovascular Disease: Analysis on Association


title: Coronavirus-2019. General considerations/ Coronavirus-2019. Consideraciones Generales

text: According to what was published by the WHO (World Health Organization), a first case of acute respiratory infection, of unknown origin, appeared in the province of HUBEI, CHINA, in the city of WUHAN, (December 2019). After having ruled out other etiological agents, the isolation of a new coronavirus (7-01-2020) was achieved, which was called new coronavirus (nCOV, COVID-19), currently named SARS-CoV-2. Coronaviruses, being important pathogens, can infect the respiratory, gastrointestinal, hepatic, and nervous systems of humans and birds, livestock, bats, mice, and other wild animals. Since the outbreaks of SARS (Severe Acute Respiratory Syndrome) in 2002 and MERS (Middle East Respiratory Syndrome) in 2012, the transmission of these viruses between humans and animals has been demonstrated.


title: Covid-19 Pandemic in relation to levels of Pollution with PM2.5 and Ambient Salinity. An Environmental Wake-up Call

text: ABSTRACT INTRODUCTION: Covid-19 infection continues to be a source of great loss of life and global suffering, necessitating national lockdowns. There are however some countries and cities which appear to have contained the pandemic. Common to these countries are environmental factors including the levels of particulate matter (PM2.5) and ambient salinity. METHOD: PM2.5 and ambient salinity were assessed in a number of cities, differentially affected by Covid-19 infection. The cities chosen to be assessed were divided into two groups. The first group included cities having significantly high rates of Covid-19 infection, while the second group consisted of coastal cities or small island countries, all of which have low rates of Covid-19 infection. Minimum and maximum levels of PM2.5 were obtained from the Air Quality Index, one month before and one month after statutory lockdown. Salinity levels were obtained from a study that assessed chloride ion wet deposition, a surrogate for ambient salinity. RESULTS: One month prior to the statutory national lock-down or mandatory restrictions, there appear to be high levels of particulate matter, PM2.5 (min-max 67.4 - 118.7 AQI), in countries which had a high incidence of Covid-19 infection compared to lower levels in countries that have contained the infection (min-max 45.6 - 79.8) (p<0.046). One month after national restrictions there still appeared to be higher levels of particulate matter, PM2.5 (min-max 51 - 90.5 AQI), in countries which had a high incidence of Covid-19 infection compared to countries that have contained the infection (min-max 42.7 - 69.5 AQI) but this was not statistically significant. There seemed to be an inverse relationship between Covid-19 infection and ambient salinity levels. Countries that were spared high Covid-19 infection rates, besides their geographical isolation, also have higher ambient salinity levels (124 - 617mgCl/m2/TAG) compared to salinity levels noted in countries with high Covid-19 rates of infection (28.4 - 162. mgCl/m2/TAG) (p<0.003). CONCLUSION: High levels of PM2.5 in the presence of low ambient salinity may increase the risk of Covid-19 infection in the population. Addressing these two environmental factors may attenuate the severity of the pandemic. Keywords: Covid-19, environmental factors, PM2.5, ambient salinity.


title: Impact of the COVID-19 – a regional blood center’s perspective

text: Abstract The rapid evolution of the novel coronavirus pneumonia (COVID-19) from Wuhan, Hebei, China to a global pandemic has caused significant impact to healthcare systems worldwide and disruption to daily lives Every country has been putting in numerous measures and efforts to control the disease spread and manage all the patients that need treatment By mid-April, the number of confirmed cases have reached 1 9 million and over 123,000 deaths are reported 1 However, it has yet to be seen when the pandemic could be under control and treatment becomes effective


title: Superior anticoagulation strategies for renal replacement therapy in critically ill patients with COVID-19: a cohort study

text: Background Coronavirus disease 2019 (COVID-19) patients who are admitted to intensive care units (ICU) have a high risk of requiring renal replacement therapy (RRT) due to acute kidney injury (AKI). Concomitantly, COVID-19 patients exhibit a state of hypercoagulability that can affect circuit lifespan. An optimal anticoagulation strategy is therefore needed in order to maintain circuit patency and therapeutic efficiency of RRT. Methods Retrospective single-centre cohort study on 71 critically ill COVID-19 patients at the University of Freiburg Medical Center. Included were all patients aged 18 years and older with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection that were admitted to ICU between February 26 and May 21, 2020. We collected data on the COVID-19 disease course, AKI, RRT, thromboembolic events and anticoagulation. Primary outcome of the study was the effect of different anticoagulation strategies during RRT on extracorporeal circuit lifespans. Results Anticoagulation during continuous veno-venous haemodialysis (CVVHD) was performed with unfractionated heparin (UFH) or citrate. Mean treatment time in the UFH group was 21.3h (SEM: {+/-}5.6h). Mean treatment time in the citrate group was 45.6h (SEM: {+/-}2.7h). Citrate anticoagulation prolonged treatment duration significantly by 24.4h (p=0.0014). Anticoagulation during sustained low-efficiency daily dialysis (SLEDD) was performed with UFH, argatroban or low molecular weight heparin (LMWH). Mean dialysis time with UFH was 8.1h (SEM: {+/-}1.3h), argatroban 8.0h (SEM: {+/-}0.9h) and LMWH 11.8h (SEM: {+/-}0.5h). Compared to UFH and argatroban, LMWH significantly prolonged treatment times by 3.7h (p=0.0082) and 3.8h (p=0.0024), respectively. Conclusions UFH fails to prevent early clotting events in dialysis circuits. For patients, who do not require an effective systemic anticoagulation, regional citrate dialysis is the most effective strategy in our cohort. For patients, who require an effective systemic anticoagulation treatment, the usage of LMWH results in the longest circuit life spans.


title: Variation of positiveness to enhance testing of specimens during an epidemic

text: Rapid testing of appropriate specimens from patients suspected for a disease during an epidemic, such as the current Coronavirus outbreak, is of a great importance for the disease management and control. We propose a method to enhance processing large amounts of collected samples. The method is based on mixing samples in testing tubes in a specific configuration, as opposed to testing single samples in each tube, and ac- counting for natural virus amounts in infected patients from variation of positiveness in test tubes. To illustrate the efficiency of the suggested method we carry out numerical tests for actual scenarios under various tests. Applying the proposed method enhances the number of tests by order of magnitudes, where all positives are identified with no false negatives, and the effective testing time can be reduced drastically even when the uncertainty in the test is relatively high.


title: Mechanistic insights into ventricular arrhythmogenesis of hydroxychloroquine and azithromycin for the treatment of COVID-19

text: Aims We investigate mechanisms for potential pro-arrhythmic effects of hydroxychloroquine (HCQ) alone, or combined with azithromycin (AZM), in Covid-19 management supplementing the limited available experimental cardiac safety data. Methods We integrated patch-clamp studies utilizing In Vitro ProArrhythmia Assay (CiPA) Schema IC50 paradigms, molecular modelling, cardiac multi-electrode array and voltage (RH237) mapping, ECG studies, and Ca2+ (Rhod-2 AM) mapping in isolated Langendorff-perfused guinea-pig hearts with human in-silico ion current modelling. Results HCQ blocked IKr and IK1 with IC50s (10±0.6 and 34±5.0 μM) within clinical therapeutic ranges, INa and ICaL at higher IC50s, leaving Ito and IKs unaffected. AZM produced minor inhibition of INa, ICaL, IKs, and IKr,, sparing IK1 and Ito. HCQ+AZM combined inhibited IKr and IK1 with IC50s of 7.7±0.8 μM and 30.4±3.0 μM, sparing INa, ICaL and Ito. Molecular modelling confirmed potential HCQ binding to hERG. HCQ slowed heart rate and ventricular conduction. It prolonged PR, QRS and QT intervals, and caused prolonged, more heterogeneous, action potential durations and intracellular Ca2+ transients. These effects were accentuated with combined HCQ+AZM treatment, which then elicited electrical alternans, re-entrant circuits and wave break. Modelling studies attributed these to integrated HCQ and AZM actions reducing IKr and IK1, thence altering cell Ca2+ homeostasis. Conclusions Combined HCQ+AZM treatment exerts pro-arrhythmic ventricular events by synergetically inhibiting IKr, IKs with resulting effects on cellular Ca2+ signalling, and action potential propagation and duration. These findings provide an electrophysiological basis for recent FDA cardiac safety guidelines cautioning against combining HCQ/AZM when treating Covid-19.


title: Relevance of enriched expression of SARS-CoV-2 binding receptor ACE2 in gastrointestinal tissue with pathogenesis of digestive symptoms, diabetes-associated mortality, and disease recurrence in COVID-19 patients

text: Introduction COVID-19, is caused by a new strain of coronavirus called SARS-coronavirus-2 (SARS-CoV-2), which is a positive sense single strand RNA virus. In humans, it binds to angiotensin converting enzyme 2 (ACE2) with the help a structure on its surface called the S-spike. COVID-19 poses intriguing issues with imperative relevance to clinicians. The pathogenesis of GI symptoms, diabetes-associated mortality, and disease recurrence in COVID-19 are of particular relevance because they cannot be sufficiently explained from the existing knowledge of the viral diseases. Tissue specific variation of ACE2 expression in healthy individuals can help in understanding the pathophysiological basis the aforementioned collection of symptoms. Materials and Methods The data were downloaded from the Human Protein Atlas available at (https://www.proteinatlas.org/search/ACE2) and the tissue specific expression (both mRNA and protein) of ACE2 as yielded from the studies with RNA sequencing and immunohistochemistry (IHC) was analyzed as a function of the various components of the digestive tract. A digestive system specific functional enrichment map of ACE2 gene was created using g:profiler (https://biit.cs.ut.ee/gprofiler/gost) utility and the data were visualized using Cytoscape software, version 3.7.2 (https://cytoscape.org/). Results The correlated expression (genomic and proteomic) of ACE2 (to which SARS-CoV-2 binds through the S-spike) was found to be enriched in the lower gastrointestinal tract (GIT) (highest in small intestine, followed by colon and rectum), and was undetectable in the upper GIT components: mouth cavity (tongue, oral mucosa, and salivary glands), esophagus, and stomach. High expression of ACE2 was noted in the glandular cells as well as in the enterocytes in the lining epithelium (including brush border epithelium). Among other digestive system organs, gallbladder (GB) showed high expression of ACE2 in glandular cells, while any protein expression was undetectable in liver and pancreas. Conclusions Based on the findings of this study and supportive evidence from the literature we propose that a SARS-CoV-2 binding with ACE2 mediates dysregulation of the sodium dependent nutrient transporters and hence may be a plausible basis for the digestive symptoms in COVID-19 patients. ACE2 mediated dysregulation of sodium dependent glucose transporter (SGLT1 or SLC5A1) in the intestinal epithelium also links it to the pathogenesis of diabetes mellitus which can be a possible reason for the associated mortality in COVID-19 patients with diabetes. High expression of ACE2 in mucosal cells of the intestine and GB make these organs potential sites for the virus entry and replication. Continued replication of the virus at these ACE2 enriched sites may be a basis for the disease recurrence reported in some, thought to be cured, patients. Highlights SARS-CoV-2 binding receptor ACE2 expression is enriched in human intestine ACE2 regulates neutral amino acid (B0AT1) and glucose transporter (SGLT1) in intestinal epithelium Mucus secreted from GI cells may protect SARS-CoV-2 from harsh pH levels of the digestive juices Continued replication of SARS-CoV-2 in GI cells may cause disease recurrence Graphical Abstract


title: An interpretable mortality prediction model for COVID-19 patients

text: The sudden increase in COVID-19 cases is putting high pressure on healthcare services worldwide. At this stage, fast, accurate and early clinical assessment of the disease severity is vital. To support decision making and logistical planning in healthcare systems, this study leverages a database of blood samples from 485 infected patients in the region of Wuhan, China, to identify crucial predictive biomarkers of disease mortality. For this purpose, machine learning tools selected three biomarkers that predict the mortality of individual patients more than 10 days in advance with more than 90% accuracy: lactic dehydrogenase (LDH), lymphocyte and high-sensitivity C-reactive protein (hs-CRP). In particular, relatively high levels of LDH alone seem to play a crucial role in distinguishing the vast majority of cases that require immediate medical attention. This finding is consistent with current medical knowledge that high LDH levels are associated with tissue breakdown occurring in various diseases, including pulmonary disorders such as pneumonia. Overall, this Article suggests a simple and operable decision rule to quickly predict patients at the highest risk, allowing them to be prioritized and potentially reducing the mortality rate.


title: Molecular mechanism of action of repurposed drugs and traditional Chinese medicine used for the treatment of patients infected with COVID-19: A systematic review

text: The emergence of COVID-19 as a pandemic has resulted in the need for urgent development of vaccines and drugs and the conduction of clinical trials to fight the outbreak. Because of the time constraints associated with the development of vaccines and effective drugs, drug repurposing and other alternative treatment methods have been used to treat patients that have been infected by the SARS-CoV-2 virus and have acquired COVID-19. In this systematic review, we provide an overview of the molecular mechanism of action of repurposed drugs or alternative treatment medicines used to attenuate COVID-19 disease. The research articles or grey literature, including theses, government reports, and official news online, were identified from 4 databases and 1 search engine. The full content of a total of 160 articles that fulfilled our inclusion criteria was analyzed and information about 6 drugs (ritonavir, lopinavir, oseltamivir, remdesivir, favipiravir, and chloroquine) and 4 traditional Chinese medicines (Shuang Huang Lian Kou Fu Ye, TCM combination of Bu Huan Jin Zheng Qi San and Da Yuan Yin, Xue Bi Jing Injection and Qing Fei Pai Du Tang) were extracted. All of the drug treatment options depend on the ability of the drug to inhibit the proliferation of the SARS-CoV-2 virus by binding to enzyme active sites, viral chain termination, or triggering of the molecular pathway, whereas traditional Chinese medicine has a pivotal role in triggering the inflammation pathway, such as the neuraminidase blocker, to fight the SARS-CoV-2 virus. This review provides an insight to experimental validation of drugs and alternative medicine used for the treatment and control of COVID-19.


Antirheumatic in SARS-CoV-2: benefit or risk?


title: Estimating the maximum daily number of incident COVID-19 cases manageable by a healthcare system

text: The COVID-19 Acute and Intense Resource Tool (CAIC-RT) is an interactive online tool capable of estimating the maximum daily number of incident COVID- 19 cases that a healthcare system could manage given age-based case distribution and severity.


title: State heterogeneity of human mobility and COVID-19 epidemics in the European Union

text: Human mobility was associated with epidemic changes of coronavirus disease 2019 (COVID-19) in China, where strict public health interventions reduced human mobility and COVID-19 epidemics. But its association with COVID-19 epidemics in the European Union (EU) is unclear. In this quasi-experimental study, we modelled the temporal trends in human mobility and epidemics of COVID-19 in the 27 EU states between January 15 and May 9, 2020. COVID-19 and human mobility had 3 trend-segments, including an upward trend in COVID-19 daily incidence and a downward trend in most human mobilities in the middle segment. Compared with the EU states farther from Italy, the state-wide lockdown dates were more likely linked to turning points of human mobilities in the EU states closer to Italy, which were also more likely linked to second turning points of COVID-19 epidemics. Among the examined human mobilities, the second turning points in driving mobility and the first turning points in parks mobility were the best factors that connected lockdown dates and COVID-19 epidemics in the EU states closer to Italy. Our findings highlight the state- and mobility-heterogeneity in the associations of public health interventions and human mobility with changes of COVID-19 epidemics in the EU states.


title: Global Genetic Cartography of Urban Metagenomes and Anti-Microbial Resistance

text: Although studies have shown that urban environments and mass-transit systems have distinct genetic profiles, there are no systematic worldwide studies of these dense, human microbial ecosystems. To address this gap in knowledge, we created a global metagenomic and antimicrobial resistance (AMR) atlas of urban mass transit systems from 60 cities, spanning 4,728 samples and 4,424 taxonomically-defined microorganisms collected for three years. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance markers, and novel genetic elements, including 10,928 novel predicted viral species, 1302 novel bacteria, and 2 novel archaea. Urban microbiomes often resemble human commensal microbiomes from the skin and airways, but also contain a consistent “core” of 31 species which are predominantly not human commensal species. Samples show distinct microbial signatures which may be used to accurately predict properties of their city of origin including population, proximity to the coast, and taxonomic profile. These data also show that AMR density across cities varies by several orders of magnitude, including many AMRs present on plasmids with cosmopolitan distributions. Together, these results constitute a high-resolution, global metagenomic atlas, which enables the discovery of new genetic components of the built human environment, highlights potential forensic applications, and provides an essential first draft of the global AMR burden of the world’s cities.


title: A Case of Coronavirus Disease 2019 With Concomitant Acute Cerebral Infarction and Deep Vein Thrombosis

text: We report a case of a 75-year-old woman diagnosed with severe coronavirus disease 2019 (COVID-19) complicated by acute cerebral infarction. The patient was admitted to our hospital on 5 February 2020 with severe COVID-19. On 20 February 2020, she was diagnosed with concomitant acute cerebral infarction via head computed tomography (CT) and deep vein thrombosis in both lower limbs. After symptomatic and supportive treatments, the patient was discharged on 13 March 2020. She will comply with quarantine for another 2 weeks and receive rehabilitation training from a specialist doctor. Cerebral infarction should be considered and promptly managed in patients with COVID-19.


title: Effectiveness of Ivermectin as add-on Therapy in COVID-19 Management (Pilot Trial)

text: Background: To date no effective therapy has been demonstrated for COVID-19. In vitro, studies indicated that ivermectin (IVM) has antiviral effect. Objectives: To assess the effectiveness of ivermectin (IVM) as add-on therapy to hydroxychloroquine (HCQ) and azithromycin (AZT) in treatment of COVID-19. Methods: This Pilot clinical trial conducted on hospitalized adult patients with mild to moderate COVID-19 diagnosed according to WHO interim guidance. Sixteen Patients received a single dose of IVM 200Mcg /kg on admission day as add on therapy to hydroxychloroquine ( HCQ)and Azithromycin (AZT) and were compared with 71 controls received HCQ and AZT matched in age, gender, clinical features, and comorbidities. The primary outcome was percentage of cured patients, defined as symptoms free to be discharged from the hospital and 2 consecutive negative PCR test from nasopharyngeal swabs at least 24 hours apart. The secondary outcomes were time to cure in both groups and evaluated by measuring time from admission of the patient to the hospital till discharge. Results: Of 87 patients included in the study,t he mean age {+/-} SD (range) of patients in the IVM group was similar to controls [44.87 {+/-} 10.64 (28-60) vs 45.23 {+/-} 18.47 (8-80) years, p=0.78] Majority of patients in both groups were male but statistically not significant [11(69%) versus 52 (73%), with male: female ratio 2.21 versus 2.7-, p=0.72) All the patients of IVM group were cured compared with the controls [ 16 (100 %) vs 69 (97.2 %)]. Two patients died in the controls. The mean time to stay in the hospital was significantly lower in IVM group compared with the controls (7.62 {+/-}2.75 versus 13.22 {+/-}.90 days, p=0.00005, effect size= 0.82). No adverse events were observed Conclusions : Add-on use of IVM to HCQ and AZT had better effectiveness, shorter hospital stay, and relatively safe compared with controls. however, a larger prospective study with longer follow up may be needed to validate these results.


title: Pandemics, tourism and global change: a rapid assessment of COVID-19

text: The novel coronavirus (COVID-19) is challenging the world With no vaccine and limited medical capacity to treat the disease, nonpharmaceutical interventions (NPI) are the main strategy to contain the pandemic Unprecedented global travel restrictions and stay-at-home orders are causing the most severe disruption of the global economy since World War II With international travel bans affecting over 90% of the world population and wide-spread restrictions on public gatherings and community mobility, tourism largely ceased in March 2020 Early evidence on impacts on air travel, cruises, and accommodations have been devastating While highly uncertain, early projections from UNWTO for 2020 suggest international arrivals could decline by 20 to 30% relative to 2019 Tourism is especially susceptible to measures to counteract pandemics because of restricted mobility and social distancing The paper compares the impacts of COVID-19 to previous epidemic/pandemics and other types of global crises and explores how the pandemic may change society, the economy, and tourism It discusses why COVID-19 is an analogue to the ongoing climate crisis, and why there is a need to question the volume growth tourism model advocated by UNWTO, ICAO, CLIA, WTTC and other tourism organizations


title: Downsides of face masks and possible mitigation strategies: a systematic review and meta-analysis

text: Objective To identify, appraise, and synthesise studies evaluating the downsides of wearing facemasks in any setting. We also discuss potential strategies to mitigate these downsides. Methods PubMed, Embase, CENTRAL, EuropePMC were searched (inception-18/5/2020), and clinical registries were searched via CENTRAL. We also did forward-backward citation search of the included studies. We included randomised controlled trials and observational studies comparing facemask use to any active intervention or to control. Two author pairs independently screened articles for inclusion, extracted data and assessed the quality of included studies. The primary outcomes were compliance, discomforts, harms, and adverse events of wearing facemasks. Findings We screened 5471 articles, including 37 (40 references); 11 were meta-analysed. For mask wear adherence, 47% more people wore facemasks in the facemask group compared to control; adherence was significantly higher (26%) in the surgical/medical mask group than in N95/P2 group. The largest number of studies reported on the discomfort and irritation outcome (20-studies); fewest reported on the misuse of masks, and none reported on mask contamination or risk compensation behaviour. Risk of bias was generally high for blinding of participants and personnel and low for attrition and reporting biases. Conclusion There are insufficient data to quantify all of the adverse effects that might reduce the acceptability, adherence, and effectiveness of face masks. New research on facemasks should assess and report the harms and downsides. Urgent research is also needed on methods and designs to mitigate the downsides of facemask wearing, particularly the assessment of alternatives such as face shields.


title: Magnetic Bead-Quantum Dot (MB-Qdot) CRISPR Assay for Instrument-Free Viral DNA Detection

text: We have developed a novel detection system which couples CRISPR-Cas recognition of target sequences, Cas mediated nucleic acid probe cleavage, and quantum dots as highly sensitive reporter molecules for instrument-free detection of viral nucleic acid targets. After target recognition and Cas mediated cleavage of biotinylated ssDNA probe molecules, the probe molecules are bound to magnetic particles. A complimentary ssDNA oligonucleotide quantum dot conjugate is then added, which only hybridizes to un-cleaved probes on the magnetic beads. After separation of hybridized from unhybridized quantum dot conjugates by magnetic sequestration, the signal is measured fluorometrically to provide a signal proportional to the cleaved probes and therefore the amount of target nucleic acid. To demonstrate the power of this assay, a 250 bp DNA target sequence matching a portion of the African swine fever virus (ASFV) genome is used and a detection limit of ~0.5 nM is achieved without target amplification using a simple portable ultraviolet flashlight. The positive samples are readily confirmed by visual inspection, completely avoiding the need for complicated devices and instruments. This work establishes the feasibility of a simple, instrument free assay for rapid nucleic acid screening in both hospitals and point-of-care settings.


title: History of investigation and current classification of Coronaviruses (Nidovirales: Coronaviridae)/ ИСТОРИЯ ИЗУЧЕНИЯ И СОВРЕМЕННАЯ КЛАССИФИКАЦИЯ КОРОНАВИРУСОВ (NIDOVIRALES: CORONAVIRIDAE)

text: An epidemic of COVID-19 (Coronavirus disease 2019) etiologically associated with the SARS-CoV-2 (Severe acute respiratory syndrome-related coronavirus 2) that occurred at the turn of 2019–2020 firstly in Wuhan (Hubei province of China) and then spread to many countries around the world rose a new wave of interest to coronaviruses. The first coronaviruses – members of the Coronaviridae family belonging to the order Nidovirales — were discovered in the first half of the last century. The first human coronavirus, HCoV-B814, was isolated in 1965 that was not preserved in available virological collections. Over the last time, old-fashioned names and terms have been overlapped. By the beginning of the XXI century coronaviruses posed a serious veterinary problem but it was believed that epidemic coronaviruses were not among highly dangerous viruses. Scientific community had to revise such views first in 2002 when SARS-CoV (Severe acute respiratory syndrome-related coronavirus) was transferred to human population in the Southeast Asia from bats, and then in 2012 when natural foci of the MERS-CoV (Middle East respiratory syndrome-related coronavirus) were found on the territory of the Arabian Peninsula. Due to an increased interest in coronaviruses, a large number of new Coronaviridae members was discovered in the first two decades of the XXI century, which required to revise its taxonomic structure several times. This review is aimed at outlining a history of investigating coronaviruses and their current classification that was shaped in early 2020 in accordance to the last recommendations of the International Committee on Taxonomy of Viruses.


title: Practical measures to prevent COVID-19: A mini-review

text: In view of the global COVID-19 pandemic, this study focuses on the most up-to-date epidemiology, transmission, clinical manifestations, effective management, prevention and maintaining social distancing worldwide. The current outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19 disease was first reported from Wuhan, China, in December, 2019. Till now this pandemic had spread to 209 countries and territories around the world and 2 international conveyances with 1,455,519 confirmed cases, including 83,664 deaths, as of April 08, 2020, so the World Health Organization declared it as a Public Health Emergency of worldwide (https://www.worldometers.info/coronavirus/). The main clinical manifestations are included fever, coughing, sore throat, fatigue, headache, diarrhea, hemoptysis, trouble breathing, blue lips or face, persistent pain or pressure in the chest, confusion and excessive drowsiness. Preventive measures such as; masks, frequent hand washing, staying at home, avoid public contact and quarantines are being recommended for reducing the transmission. To date, no specific antiviral treatment is proven yet. The countries with a high risk of infection, they need proper awareness and management for good protection.


title: Indomethacin has a potent antiviral activity against SARS CoV-2 in vitro and canine coronavirus in vivo

text: Background The outbreak of SARS CoV-2 has caused ever-increasing attention and public panic all over the world. Currently, there is no specific treatment against the SARS CoV-2. Therefore, identifying effective antiviral agents to combat the disease is urgently needed. Previous studies found that indomethacin has the ability to inhibit the replication of several unrelated DNA and RNA viruses, including SARS-CoV. Methods SARS CoV-2 pseudovirus-infected African green monkey kidney VERO E6 cells treated with different concentrations of indomethacin or aspirin at 48 hours post infection (p.i). The level of cell infection was determined by luciferase activity. Anti-coronavirus efficacy in vivo was confirmed by evaluating the time of recovery in canine coronavirus (CCV) infected dogs treated orally with 1mg/kg body weight indomethacin. Results We found that indomethacin has a directly and potently antiviral activity against the SARS CoV-2 pseudovirus (reduce relative light unit to zero). In CCV-infected dogs, recovery occurred significantly sooner with symptomatic treatment + oral indomethacin (1 mg/kg body weight) daily treatments than with symptomatic treatment + ribavirin (10-15 mg/kg body weight) daily treatments (P =0.0031), but was not significantly different from that with symptomatic treatment + anti-canine coronavirus serum + canine hemoglobin + canine blood immunoglobulin + interferon treatments (P =0.7784). Conclusion The results identify indomethacin as a potent inhibitor of SARS CoV-2.


title: Semantic and geographical analysis of Covid-19 trials reveals a fragmented clinical research landscape likely to impair informativeness.

text: Background. The unprecedented impact of the Covid-19 pandemics on modern society has ignited a "gold rush" for effective treatment and diagnostic strategies, with a significant diversion of economical, scientific and human resources towards dedicated clinical research. We aimed to describe trends in this rapidly changing landscape to inform adequate resource allocation. Methods. We developed informatic tools (Covid Trial Monitor) to analyze in real time growth rate, geographical distribution and characteristics of Covid-19 related trials. We defined structured semantic ontologies with controlled vocabularies to categorize trial interventions, study endpoints and study designs. Data and analyses are publicly available at https://bioinfo.ieo.it/shiny/app/CovidCT Results. We observe a clear prevalence of monocentric trials with highly heterogeneous endpoints and a significant disconnect between geographic distribution and disease prevalence, implying that most countries would need to recruit unrealistic percentages of their total prevalent cases to fulfill enrolment. Conclusions. This geographically and methodologically incoherent growth sheds doubts on the actual feasibility of locally reaching target sample sizes and the probability of most of these trials providing reliable and transferable result. We call for the harmonization of clinical trial design criteria for Covid19 and the increased use of larger master protocols incorporating elements of adaptive designs. Covid Trial Monitor identifies critical issues in current Covid19-related clinical research and represents a useful resource for researchers and policymakers to improve the quality and efficiency of related trials


title: Clinical Characteristics, Risk Factors and Outcomes Among the First Consecutive 1,096 Patients Diagnosed with COVID-19: The Kuwait Experience

text: Background In Kuwait, prior to the first case of COVID-19 being reported in the country, mass screening of incoming travelers from countries with known outbreaks was performed and resulted in the first identified cases in the country. All COVID-19 cases at the time and subsequently after, were transferred to a single center, Jaber Al-Ahmad Al-Sabah Hospital, where the patients received standardized investigations and treatments. The objective of this study was to characterize the demographics, clinical manifestations and outcomes in this unique patient population. Methods This retrospective cohort study was conducted between 24th February 2020 and 20th April 2020. All consecutive patients in the entire State of Kuwait diagnosed with COVID-19 according to WHO guidelines and admitted to Jaber Al-Ahmad Al-Sabah Hospital were recruited. Patients received standardized investigations and treatments. Multivariable analysis was used to determine the associations between risk factors and outcomes. Findings Of 1096 patients, the median age was 41 years and 81% of patients were male. Most patients were asymptomatic on admission (49.5%), 69.4% had no signs of infection and 94.6% were afebrile. Only 3.6% of patients required an ICU admission and 1.7% were dead at the study cutoff date. On multivariate analysis, the risk factors found to be significantly associated with admission to intensive care were age above 50 years old, a qSOFA score above 0, smoking, elevated CRP and elevated procalcitonin levels. Asthma, smoking and elevated procalcitonin levels correlated significantly with mortality in our cohort. Interpretation To our knowledge, this is the first large retrospective cohort study observing the characteristics of the initial consecutive COVID-19 patients of an entire country. Further, large proportion of asymptomatic patients provides novel insights into the clinical features of patients with milder disease.


Prone Cardiopulmonary Resuscitation: A Rapid Scoping and Expanded Grey Literature Review for the COVID-19 Pandemic Aim To rapidly identify and summarize the available science on prone resuscitation. To determine the value of undertaking a systematic review on this topic; and to identify knowledge gaps to aid future research, education and guidelines. Methods This review was guided by specific methodological framework and reporting items (PRISMA-ScR). We included studies, cases and grey literature regarding prone position and CPR/cardiac arrest. The databases searched were MEDLINE, Embase, CINAHL, Cochrane CENTRAL, Cochrane Database of Systematic Reviews, Scopus and Google Scholar. Expanded grey literature searching included internet search engine, targeted websites and social media. Results Of 453 identified studies, 24 (5%) studies met our inclusion criteria. There were four prone resuscitation-relevant studies examining: blood and tidal volumes generated by prone compressions; prone compression quality metrics on a manikin; and chest computed tomography scans for compression landmarking. Twenty case reports/series described the resuscitation of 25 prone patients. Prone compression quality was assessed by invasive blood pressure monitoring, exhaled carbon dioxide and pulse palpation. Recommended compression location was zero-to-two vertebral segments below the scapulae. Twenty of 25 cases (80%) survived prone resuscitation, although few cases reported long term outcome. Seven cases described full neurological recovery. Conclusion This scoping review did not identify sufficient evidence to justify a systematic review or modified resuscitation guidelines. It remains reasonable to initiate resuscitation in the prone position if turning the patient supine would lead to delays or risk to providers or patients. Prone resuscitation quality can be judged using end-tidal CO2, and arterial pressure tracing, with patients turned supine if insufficient. Key words CPR, prone, cardiopulmonary resuscitation, Scoping review, Resuscitation, covid-19, SARS-CoV-2


title: A model to predict SARS-CoV-2 infection based on the first three-month surveillance data in Brazil.

text: Background: COVID-19 diagnosis is a critical problem, mainly due to the lack or delay in the test results. We aimed to obtain a model to predict SARS-CoV-2 infection in suspected patients reported to the Brazilian surveillance system. Methods: We analyzed suspected patients reported to the National Surveillance System that corresponded to the following case definition: patients with respiratory symptoms and fever, who traveled to regions with local or community transmission or who had close contact with a suspected or confirmed case. Based on variables routinely collected, we obtained a multiple model using logistic regression. The area under the receiver operating characteristic curve (AUC) and accuracy indicators were used for validation. Results: We described 1468 COVID-19 cases (confirmed by RT-PCR) and 4271 patients with other illnesses. With a data subset, including 80% of patients from Sao Paulo (SP) and Rio Janeiro (RJ), we obtained a function which reached an AUC of 95.54% (95% CI: 94.41% - 96.67%) for the diagnosis of COVID-19 and accuracy of 90.1% (sensitivity 87.62% and specificity 92.02%). In a validation dataset including the other 20% of patients from SP and RJ, this model exhibited an AUC of 95.01% (92.51% - 97.5%) and accuracy of 89.47% (sensitivity 87.32% and specificity 91.36%). Conclusion: We obtained a model suitable for the clinical diagnosis of COVID-19 based on routinely collected surveillance data. Applications of this tool include early identification for specific treatment and isolation, rational use of laboratory tests, and input for modeling epidemiological trends.


title: Variant analysis of SARS-CoV-2 strains in Middle Eastern countries

text: Background SARS-CoV-2 is diverging from the initial Wuhan serotype, and different variants of the virus are reported. Mapping the variant strains and studying their pattern of evolution will provide better insights into the pandemic spread Methods Data on different SARS-CoV2 for WHO EMRO countries were obtained from the Chinese National Genomics Data Center (NGDC), Genbank and the Global Initiative on Sharing All Influenza Data (GISAID). Multiple sequence alignments (MSA) was performed to study the evolutionary relationship between the genomes. Variant calling, genome and variant alignment were performed to track the strains in each country. Evolutionary and phylogenetic analysis is used to explore the evolutionary hypothesis. Findings Of the total 50 samples, 4 samples did not contain any variants. Variant calling identified 379 variants. Earliest strains are found in Iranian samples. Variant alignment indicates Iran samples have a low variant frequency. Saudi Arabia has formed an outgroup. Saudi Arabia, Qatar and Kuwait were the most evolved genomes and are the countries with the highest number of cases per million. Interpretation Iran was exposed to the virus earlier than other countries in the Eastern Mediterranean Region. Funding None


title: The impact of the coronavirus outbreak on Macao. From tourism lockdown to tourism recovery

text: Macao was one of the first cities outside China to start a gradual tourism lockdown in January 2020 due to the coronavirus outbreak. Although critical to Macao’s economy, tourism had essentially ceased by March 2020, as the city closed its borders to regional and foreign arrivals. This paper presents the key policy and health measures since Macao’s first coronavirus case in January. The city had recorded no coronavirus cases in the city in early March, but saw a second wave of imported coronavirus cases mostly as residents and non-resident workers returned from overseas. At the request of government, over 10% of Macao’s hotel room inventory had been allocated as quarantine hotels. The ‘top-down’ approach by government meant stringent policy measures consisting of border closures and health advisories were actioned immediately to stem the spread of coronavirus. The economic consequences to the casino industry, which supplies 85% of the government’s total tax revenues, have been dramatic, as casino revenues continue to spiral downwards by over 80% in both February and March. This paper presents Macao’s reaction to the coronavirus in a three-wave analogy. It is argued that the recovery wave should move to public-private consolidation and collaboration.


title: Missense variants in ACE2 are predicted to encourage and inhibit interaction with SARS-CoV-2 Spike and contribute to genetic risk in COVID-19

text: SARS-CoV-2 invades host cells via an endocytic pathway that begins with the interaction of the SARS-CoV-2 Spike glycoprotein (S-protein) and human Angiotensin-converting enzyme 2 (ACE2). Genetic variability in ACE2 may be one factor that mediates the broad-spectrum severity of SARS-CoV-2 infection and COVID-19 outcomes. We investigated the capacity of ACE2 variation to influence SARS-CoV-2 infection with a focus on predicting the effect of missense variants on the ACE2 SARS-CoV-2 S-protein interaction. We validated the mCSM-PPI2 variant effect prediction algorithm with 26 published ACE2 mutant SARS-CoV S-protein binding assays and found it performed well in this closely related system (True Positive Rate = 0.7, True Negative Rate = 1). Application of mCSM-PPI2 to ACE2 missense variants from the Genome Aggregation Consortium Database (gnomAD) identified three that are predicted to strongly inhibit or abolish the S-protein ACE2 interaction altogether (p.Glu37Lys, p.Gly352Val and p.Asp355Asn) and one that is predicted to promote the interaction (p.Gly326Glu). The S-protein ACE2 inhibitory variants are expected to confer a high degree of resistance to SARS-CoV-2 infection whilst the S-protein ACE2 affinity enhancing variant may lead to additional susceptibility and severity. We also performed in silico saturation mutagenesis of the S-protein ACE2 interface and identified a further 38 potential missense mutations that could strongly inhibit binding and one more that is likely to enhance binding (Thr27Arg). A conservative estimate places the prevalence of the strongly protective variants between 12-70 per 100,000 population but there is the possibility of higher prevalence in local populations or those underrepresented in gnomAD. The probable interplay between these ACE2 affinity variants and ACE2 expression polymorphisms is highlighted as well as gender differences in penetrance arising from ACE2’s situation on the X-chromosome. It is also described how our data can help power future genetic association studies of COVID-19 phenotypes and how the saturation mutant predictions can help design a mutant ACE2 with tailored S-protein affinity, which may be an improvement over a current recombinant ACE2 that is undergoing clinical trial. Key results 1 ACE2 gnomAD missense variant (p.Gly326Glu) and one unobserved missense mutation (Thr27Arg) are predicted to enhance ACE2 binding with SARS-CoV-2 Spike protein, which could result in increased susceptibility and severity of COVID-19 3 ACE2 missense variants in gnomAD plus another 38 unobserved missense mutations are predicted to inhibit Spike binding, these are expected to confer a high degree of resistance to infection The prevalence of the strongly protective variants is estimated between 12-70 per 100,000 population but higher prevalence may exist in local populations or those underrepresented in gnomAD A strategy to design a recombinant ACE2 with tailored affinity towards Spike and its potential therapeutic value is presented The predictions were extensively validated against published ACE2 mutant binding assays for SARS-CoV Spike protein


title: Why Learning on the Move: Intersecting Research Pathways for Mobility, Learning and Teaching

text: Mobility provides the fabric of everyday life but is rarely considered part of learning and is almost never used as relevant, experiential content in teaching. This special issue integrates ideas and efforts across different fields into a more unified framework to study and design for what we call Learning on the Move. Approaches used in these studies reflect various ontological and epistemological standpoints, especially with regard to the role of moving bodies, place, and lands/waters in learning, teaching, and development. The heterogeneity of approaches in this special issue potentially helps us to see the complexity of human, more-than-human, and technological relations across time. The specificity of each project necessarily foregrounds certain aspects of activity and history, while backgrounding others. Rather than casting this as problematic, we see this heterogeneity as an opportunity to generate dialogue across research programs that are guided by frameworks of power, historicity, relationality, respect, reciprocity, and accountability. We also take this as an opportunity to raise questions about historical, present-day, and future relationships to lands/waters, place, socio-ecological systems, and socio-technical arrangements. At a practical level, this means having conversations about the differences and similarities between ontological and epistemological conceptions of time, space, place, and lands/waters when studying or designing for Learning on the Move. We anticipate and acknowledge that at times our conceptions of Learning on the Move may align and at other times may be incommensurable.


title: An "Infodemic": Leveraging High-Volume Twitter Data to Understand Public Sentiment for the COVID-19 Outbreak

text: Background: Twitter has been used to track trends and disseminate health information during viral epidemics. On January 21, 2020, the CDC activated its Emergency Operations Center and the WHO released its first situation report about coronavirus disease 2019 (COVID-19), sparking significant media attention. How Twitter content and sentiment has evolved in the early stages of any outbreak, including the COVID-19 epidemic, has not been described. Objective: To quantify and understand early changes in Twitter activity, content, and sentiment about the COVID-19 epidemic. Design: Observational study. Setting: Twitter platform. Participants: All Twitter users who created or sent a message from January 14th to 28th, 2020. Measurements: We extracted tweets matching hashtags related to COVID-19 and measured frequency of keywords related to infection prevention practices, vaccination, and racial prejudice. We performed a sentiment analysis to identify emotional valence and predominant emotions. We conducted topic modeling to identify and explore discussion topics over time. Results: We evaluated 126,049 tweets from 53,196 unique users. The hourly number of COVID-19-related tweets starkly increased from January 21, 2020 onward. Nearly half (49.5%) of all tweets expressed fear and nearly 30% expressed surprise. The frequency of racially charged tweets closely paralleled the number of newly diagnosed cases of COVID-19. The economic and political impact of the COVID-19 was the most commonly discussed topic, while public health risk and prevention were among the least discussed. Conclusion: Tweets with negative sentiment and emotion parallel the incidence of cases for the COVID-19 outbreak. Twitter is a rich medium that can be leveraged to understand public sentiment in real-time and target public health messages based on user interest and emotion.