title: The potential application of the traditional Chinese herb Exocarpium Citri grandis in the prevention and treatment of COVID-19

text: Huajuhong (Exocarpium Citri grandis, ECG) is a traditional Chinese herbal medicine and has been used for the treatment of respiratory diseases for hundreds of years. Recently, ECG has been listed in a traditional Chinese medicine formula in the Guidelines for the Diagnosis and Treatment of Coronavirus Disease 2019 (sixth edition) in China. To date, the effect and mechanism of ECG against respiratory diseases have not been systematically reviewed. In this paper, the researchers summarized the effects of ECG and its pharmacologically active compound naringin in functioning as an antitussive and expectorant, improving lung function, alleviating acute lung injury, attenuating pulmonary fibrosis, and enhancing antiviral immune response, so as to provide a reference for its clinical application in the prevention and treatment of multiple respiratory diseases, including coronavirus disease 2019.


title: Comparison of epidemic control strategies using agent-based simulations

text: A simulation of the dynamics of a small population is used to assess the impact of different confinement and testing strategies in the control of an epidemic. The simulation considers individuals as agents moving randomly across the habitat according to predefined urban patterns. Agents carry a simple tracing device that identifies signals emitted by other agents, recording the position and time of the encounter. The information of every device is propagated daily to an epidemic observatory based on an online graph database. Infections are simulated as stochastic processes depending on the proximity among individuals. Different epidemic control strategies are tested with and without the information of the tracing device under several scenarios. We observe that the success of the strategies strongly depends on the duration of the period of infectiousness before the presence of symptoms and the fraction of asymptomatic agents. If these values are high, strategies based on the presence of symptoms or on testing campaigns can hardly contain the epidemic. Strategies using massive confinement of the agents are able to control the epidemic at the cost of sending a large fraction of the population into quarantine. In cases with moderate and low values for these parameters, the tracing devices can provide a slightly better performance but only if a large fraction of the agents carry the device. Otherwise, the impact of these devices is found to be negligible in comparison with other strategies not using them. Finally, we provide a methodology allowing to use the information of the graph database to estimate basic parameters of the disease such as the infection probability.


title: Factor reduction of quotation with rough set on incomplete data

text: Abstract With the extensive competition in a network economy environment the quotation of different orders should be various to increase the customers’ satisfaction in terms of properties of products and complexity of manufacturing processes. The enterprises employ the customization production paradigm, where the products have similar functions and structures, and adapt to such environment. However, for this mode, the mechanism is lack of making a quotation rapidly due to the complex of product and changeable demands. Formulating the relationship between factors and quotation of an order becomes an issue concerned by academia and entrepreneurs. We present control metrics to connect with those factors and existing quotation of a product. Since a quotation of product needs a large number of parameters to represent, the control metrics can be alternative of those parameters of quotation. Then, we propose a model of quoting. The correlation between the control metrics and a quotation of product is explored. Finally, a reduction approach of crucial metrics is developed by rough set on incomplete data. The case study is conducted to validate the performance of the proposed method of reduction. The outcomes show that the multiple reducts can be obtained to facilitate the enterprises to make viable quotation decision from the multiple schemes in terms of their characteristics and different demands of the customers.


title: Overcoming COVID-19: What can human factors and ergonomics offer?

text: A novel coronavirus disease, named coronavirus disease 2019 or COVID-19, which sparked an outbreak in Wuhan, China in December 2019, is now a pandemic. The rapid spread of this disease from one to more than 155 regions worldwide in 2.5 months highlights the need for better preparation to manage a pandemic. In this commentary, we describe how Human Factors and Ergonomics (HFE) can contribute to the COVID-19 pandemic response. Specifically, we provide an example of how HFE methodologies informed workflow redesigns implemented as part of COVID-19 pandemic preparations in an academic pediatric ambulatory clinic. We then identify key mechanisms and areas where HFE can contribute to and improve the effectiveness of a pandemic response: Just-in-time (JIT) training development, adapting workflows and processes, restructuring teams and tasks, developing effective mechanisms and tools for communication, engaging patient and families to follow the recommended practices (e.g., social distancing, revised hospital visitation policies), identifying and mitigating barriers to implementation of plans, and learning from failures and successes to improve both the current and future pandemic responses. We recommend integrating HFE approaches and tools across health care systems, state health organizations, and the Centers for Disease Control and Prevention (CDC) as they confront this pandemic.


title: Electrically-Assisted Manufacturing for Reduction in Forging Forces of Bearing Steels

text: Abstract The aerospace industry regularly uses three high-strength steel alloys in the manufacture of their bearings: M50, M50 NiL, and Pyrowear P675. The high strength of these alloys causes increased force, friction, and temperature rise during forging operations, resulting in residual stresses and creating issues with distortion and springback in subsequent machining operations. Electrically-assisted manufacturing (EAM) has been studied for reduction or elimination of these issues in magnesium, aluminum, and titanium alloys as well as A2 tool steel and 304 stainless steel. This research determined the threshold current densities for EAM of Pyrowear P675, M50, and M50 NiL steels. Threshold current densities were determined for each material at 33, 48, and 37 A/mm2 respectively. Once the test reached this threshold a significant reduction in yield stress occurred and the samples had an increase in hardness near the exterior, the authors assess the probability of a phase change due to resistive heating during this forming operation.


title: Effects of Tocilizumab in Critically Ill Patients With COVID-19: A Quasi-Experimental Study

text: Critically ill patients with COVID-19 may suffer from a cytokine release syndrome (CRS) characterized by remarkably high levels of interleukin 6 (IL-6). We assessed the effects of tocilizumab, an IL-6 receptor antagonist, on intra-hospital mortality and development of positive cultures in patients with COVID-19 admitted to the ICU. In this study, patients with COVID 19 admitted in the ICU who were treated with tocilizumab plus standard care were enrolled and compared to controls. Main outcome: 1) intra-hospital mortality; Secondary Outcomes: 1) the need for renal replacement therapy, 2) use of antibiotics and positive culture, and 3) inflammatory and oxygenation markers. Results: There was no difference in mortality, need for renal replacement therapy, use of antibiotics or positive cultures between the two groups. The use of corticosteroids was more frequent in the treatment group. Levels of C-reactive protein (CRP) and WBC (white blood cells) counts declined significantly faster in the treatment group. Oxygenation markers rose significantly higher in patients in the tocilizumab group as compared to controls. Conclusion: tocilizumab was associated with rapid improvement in oxygenation and a faster decrease of CRP and WBC counts in patients with COVID-19 and should be evaluated as rescue therapy for patients with progressive disease


title: COVID-19 Asymptomatic Infection Estimation

text: Background: Mounting evidence suggests that there is an undetected pool of COVID-19 asymptomatic but infectious cases. Estimating the number of asymptomatic infections has been crucial to understand the virus and contain its spread, which is, however, hard to be accurately counted. Methods: We propose an approach of machine learning based fine-grained simulator (MLSim), which integrates multiple practical factors including disease progress in the incubation period, cross-region population movement, undetected asymptomatic patients, and prevention and containment strength. The interactions among these factors are modeled by virtual transmission dynamics with several undetermined parameters, which are determined from epidemic data by machine learning techniques. When MLSim learns to match the real data closely, it also models the number of asymptomatic patients. MLSim is learned from the open Chinese global epidemic data. Findings: MLSim showed better forecast accuracy than the SEIR and LSTM-based prediction models. The MLSim learned from the data of China's mainland reveals that there could have been 150,408 (142,178-157,417) asymptomatic and had self-healed patients, which is 65% (64% - 65%) of the inferred total infections including undetected ones. The numbers of asymptomatic but infectious patients on April 15, 2020, were inferred as, Italy: 41,387 (29,037 - 57,151), Germany: 21,118 (11,484 - 41,646), USA: 354,657 (277,641 - 495,128), France: 40,379 (10,807 - 186,878), and UK: 144,424 (127,215 - 171,930). To control the virus transmission, the containment measures taken by the government were crucial. The learned MLSim also reveals that if the date of containment measures in China's mainland was postponed for 1, 3, 5, and 7 days later than Jan. 23, there would be 109,039 (129%), 183,930 (218%), 313,342 (371%), 537,555 (637%) confirmed cases on June 12. Conclusions: Machine learning based fine-grained simulators can better model the complex real-world disease transmission process, and thus can help decision-making of balanced containment measures. The simulator also revealed the potential great number of undetected asymptomatic infections, which poses a great risk to the virus containment.


title: COVID-19: Review of Epidemiology and Potential Treatments Against 2019 Novel Coronavirus

text: An epidemic of extreme respiratory deterrence, pneumonia and shortness of breath, the SARS-CoV-2 viral infection began in Wuhan, Hubei Province, China in December 2019, and rapidly spread across China and beyond, with human to human transmission. On February 12, 2020, World Health Organization officially named the new coronavirus disease as coronavirus disease 19 (COVID-19). Most COVID-19 patients were diagnosed with pneumonia and many were treated using Chinese medicines and other secondary therapies. As of April 22, 2020, the total figure of infected patients has crossed 2.6 million people worldwide with over 180,000 deaths and 700,000 patients that have recovered. Preliminary reports suggest that certain drugs, such as chloroquine and antiviral nucleotide analogues such as remdesivir, which inhibit viral replication, can target the new coronavirus, although their usefulness in the clinic is still under debate. An expert US committee developed the US NIH guidelines for COVID-19 treatment, which was just released and will be regularly updated. This manuscript reviews the epidemiology, etiology, mortality, COVID-19 clinical symptoms, and potential therapeutic drugs, while highlighting the seriousness and damage-induced by SARS-CoV-2.


title: Early epidemic spread, percolation and Covid-19

text: Human to human transmissible infectious diseases spread in a population using human interactions as its transmission vector. The early stages of such an outbreak can be modeled by a graph whose edges encode these interactions between individuals, the vertices. This article attempts to account for the case when each individual entails in different kinds of interactions which have therefore different probabilities of transmitting the disease. The majority of these results can be also stated in the language of percolation theory. The main contributions of the article are: (1) Extend to this setting some results which were previously known in the case when each individual has only one kind of interactions. (2) Find an explicit formula for the basic reproduction number $R_0$ which depends only on the probabilities of transmitting the disease along the different edges and the first two moments of the degree distributions of the associated graphs. (3) Motivated by the recent Covid-19 pandemic, we use the framework developed to compute the $R_0$ of a model disease spreading in populations whose trees and degree distributions are adjusted to several different countries. In this setting, we shall also compute the probability that the outbreak will not lead to an epidemic. In all cases we find such probability to be very low if no interventions are put in place.


title: Effects of COVID-19 home confinement on physical activity and eating behaviour Preliminary results of the ECLB-COVID19 international online-survey

text: Abstract Background Public health recommendations and governmental measures during the COVID-19 pandemic have enforced numerous restrictions on daily living including social distancing, isolation and home confinement. While these measures are imperative to abate the spreading of COVID-19, the impact of these restrictions on health behaviours and lifestyle at home is undefined. Therefore, an international online survey was launched in April 2020 in seven languages to elucidate the behavioral and lifestyle consequences of COVID-19 restrictions. This report presents the preliminary results from the first thousand responders on physical activity (PA) and nutrition behaviours. Methods Thirty-five research organisations from Europe, North-Africa, Western Asia and the Americas promoted the survey through their networks to the general society, in English, German, French, Arabic, Spanish, Portugese, and Slovenian languages. Questions were presented in a differential format with questions related to responses before and during confinement conditions. Results 1047 replies (54% women) from Asia (36%), Africa (40%), Europe (21%) and other (3%) were included into a general analysis. The COVID-19 home confinement had a negative effect on all intensities of PA (vigorous, moderate, walking and overall). Conversely, daily sitting time increased from 5 to 8 hours per day. Additionally, food consumption and meal patterns (the type of food, eating out of control, snacks between meals, number of meals) were more unhealthy during confinement with only alcohol binge drink decreasing significantly. Conclusion While isolation is a necessary measure to protect public health, our results indicate that it alters physical activity and eating behaviours in a direction that would compromise health. A more detailed analysis of survey data will allow for a segregation of these responses in different age groups, countries and other subgroups which will help develop bespoke interventions to mitigate the negative lifestyle behaviors manifest during the COVID-19 confinement.


title: Lung injury in patients with or suspected COVID-19 : a comparison between lung ultrasound and chest CT-scanner severity assessments, an observational study

text: Background: Some learned societies of radiology emitted guidelines to limit or rule out chest X-ray in patients management and recommend chest CT-scanner (CCS) as the reference to assess pulmonary injury in suspected or diagnosed Covid19 (SDC) patients with signs of clinical severity. We intend to explore the place of lung ultrasound (LU) imagery to assess lung status in those latter patients, with afterthoughts on the interest of it for quick triage of patients. Methods: eChoVid is a multicentric observational study based on routinely collected data, conducted in 3 emergency units of Assistance Publique des Hopitaux de Paris. 107 SDC patients included between 19.03.2020 and 01.04.2020 had both a LU examination (LU) and a chest CT-scanner (CCS). LU consisted in scoring lesions of 8 chest zones, each scored from 0 to 3, defining a severity Global Score (GS) ranging from 0 to 24. CCS severity score was graded from 0 to 3, according to interstitial pneumonia signs extension. 14 patients had a LU by both an expert and a newly trained physician (NTP). Findings: GS shows good performances to predict CCS severity assessment of Covid19 disease categorized as Normal vs Pathologic, AUC-ROC=0.93, maximal Youden index for GS=1, with 95% sensitivity, 83% specificity. Similar performances were found for CCS categorization Normal or Minimal vs Moderate or Severe, N=90, AUC-ROC= 0.89, maximal Youden index for GS=7, with 86% sensitivity, 78% specificity. Multi-logistic regression model provided a weighted score, relating ultrasound scoring of each chest zone and CT-scanner severity score, with no significant improvement of GS. Good agreement was found between GS assessed by NTP and experts, measured by Bland & Altman method. Interpretation : GS score brings a simple tool to assess lung damages severity in SDC patients. Compared performance results between NTP and expert physician are very preliminary but opens a path towards adoption beyond the scope of ultrasound experts. LU is a good candidate for triage of SDC patients, especially useful when CT-scanners suffer from availability issues related either to overwhelmed requests or poor health infrastructure.


title: A pessoa idosa domiciliada sob distanciamento social: possibilidades de enfrentamento à covid-19/ Older adults living under social distancing: possibilities for tackling Covid-19

text: Reflete sobre a contribuição da Atenção Primária à Saúde na concretização da estratégia de proteção dos idosos em isolamento social no contexto do seu domicílio e na vigilância e monitoramento das ILPI (Instituição de Longa Permanência para Idosos), neste momento da pandemia do novo coronavirus . Recomenda ações para os cuidados em saúde na atenção primária no Brasil numa perspectiva de um trabalho articulado e integrado que garanta a proteção às pessoas idosas em todos os locais de moradia, inclusive para aquelas em situação de maior vulnerabilidade, como os residentes em instituições de longa permanência, comunidades, os de baixa renda, moradores de rua, refugiados e nômades. Sugere a implementação de política pública emergencial, que reduza os internamentos, necessidade de terapia intensiva e, principalmente, os óbitos. Propõe uma ferramenta de monitoramento dos cuidados essenciais domiciliares à saúde das pessoas idosas que possibilite mapeamento das fortalezas e fragilidades na gestão do cuidado do idoso e será um guia para as ações da APS.


title: Risk factors affecting COVID-19 case fatality rate: A quantitative analysis of top 50 affected countries

text: Background: Latest clinical data on treatment on coronavirus disease 2019 (COVID-19) indicated that older patients and those with underlying history of smoking, hypertension or diabetes mellitus might have poorer prognosis of recovery from COVID-19. We aimed to examine the relationship of various prevailing population-based risk factors in comparison with mortality rate and case fatality rate (CFR) of COVID-19. Methods: Demography and epidemiology data which have been identified as verified or postulated risk factors for mortality of adult inpatients with COVID-19 were used. The number of confirmed cases and the number of deaths until April 16, 2020 for all affected countries were extracted from Johns Hopkins University COVID-19 websites. Datasets for indicators that are fitting with the factors of COVID-19 mortality were extracted from the World Bank database. Out of about 185 affected countries, only top 50 countries were selected to be analyzed in this study. The following seven variables were included in the analysis, based on data availability and completeness: 1) proportion of people aged 65 above, 2) proportion of male in the population, 3) diabetes prevalence, 4) smoking prevalence, 5) current health expenditure, 6) number of hospital beds and 7) number of nurses and midwives. Quantitative analysis was carried out to determine the correlation between CFR and the aforementioned risk factors. Results: United States shows about 0.20% of confirmed cases in its country and it has about 4.85% of CFR. Luxembourg shows the highest percentage of confirmed cases of 0.55% but a low 2.05% of CFR, showing that a high percentage of confirmed cases does not necessarily lead to high CFR. There is a significant correlation between CFR, people aged 65 and above (p = 0.35) and diabetes prevalence (p = 0.01). However, in our study, there is no significant correlation between CFR of COVID-19, male gender (p = 0.26) and smoking prevalence (p = 0.60). Conclusion: Older people above 65 years old and diabetic patients are significant risk factors for COVID-19. Nevertheless, gender differences and smoking prevalence failed to prove a significant relationship with COVID-19 mortality rate and CFR. Keywords: Coronavirus, COVID-19, risk, epidemiology, fatality, age, diabetes


title: Seroprevalence against COVID-19 and follow-up of suspected cases in primary health care in Spain

text: Background During the coronavirus disease 2019 (COVID-19) pandemic little information has been available about patients with mild or moderate symptoms attended and followed in the primary care setting, most of whom had an unknown status for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Objectives We aim to measure the seroprevalence of antibodies against SARS-CoV-2 infection in a community sample of asymptomatic individuals and among symptomatic patients (without confirmed diagnosis) followed in a primary care setting. As a secondary objective, we estimated the proportions of symptomatic patients seeing at an emergency department (ED), hospitalized or dying, and identified the most important clinical symptoms associated with a positive infection. Methods From April 21 to April 24 2020, we selected a random sample of 600 individuals stratified by age groups, from a total population of 19,899 individuals from a community area in Barcelona (study population 1). From April 29 to May 5 2020, we also invited all the patients that had been followed by general practitioners (GPs) (study population 2). We used for both populations COVID-19 Rapid lateral flow immunoassay which qualitatively assesses the presence of patient-generated IgG and IgM in approximately 10-15 minutes. The prevalence (95% confidence intervals [CI]) of infection (past and current) was defined as the proportion of individuals with antibody seropositivity. Odds ratios (ORs) for a positive test result were estimated using logistic regression analysis. Results Three hundred and eleven asymptomatic individuals from the randomly selected sample accepted to participate in the study. The overall mean age was 43.7 years (SD 21.79, range 1-94) and 55% were women. Seventeen individuals were seropositive for IgM and/or IgG, resulting an overall prevalence of 5,47% (95% CI, 3.44-8.58). Six-hundred and thirty-four symptomatic patients were followed by GPs. The overall mean age was 46.97 years (SD 20.05, range 0-92) and 57.73% were women. Of these, 244 patients (38.49%) were seropositive for IgM and/or IgG. During the follow-up period, 27.13% of symptomatic patients attended the ED, 11.83% were hospitalized and about 2% died. Results of the multivariate logistic regression analysis showed that the OR for a positive test was significantly increased in patients who had fever (>38{degrees}C), ageusia and contact with a patient diagnosed with COVID-19. Conclusions The seroprevalence of antibodies against SARS-CoV-2 among asymptomatic individuals in the general population was lower than expected. Approximately 40% of the symptomatic patients followed by GPs during the peak months of the pandemic in Barcelona, were positive. Fever (>38{degrees}C), anosmia, ageusia and contact with a patient diagnosed with COVID-19 were associated with a positive test result.


title: Spread of the Novel Coronavirus (SARS-CoV-2): Modeling and Simulation of Control Strategies

text: The coronavirus disease 2019 (COVID-19) is spreading throughout the world and all healthcare systems are loaded beyond its capacity. The virus is named as SARS-CoV-2. In this situation, rational decisions need to be made on how the care is provided for patients with COVID-19. The Incidence report, general symptoms and readily available testing kits, different control strategies, the basic compartmental model, and some of the current research on the epidemiology of the disease are discussed and previously published models are reviewed. Modeling this disease helps in understanding the spread, and predict its future to evaluate different control strategies (Social Distancing, Contact Tracing and Hospitalization). Compartmental modeling framework is used in this work. The non-linear equations are formulated and fitted to the cumulative case and mortality data. Analytical analysis along with uncertainty analysis and sensitivity analysis is performed, and the conditions to achieve disease free equilibrium is evaluated. Finally, Different control strategies are simulated to show their importance. This paper aims to shows the advantage of mathematical modeling and their simulations in times like now, during which the COVID-19 spreading like wildfire. It also includes Pre-symptomatic and asymptomatic individuals in the modeling. The simulations are performed for the model fit to Cumulative Case and Mortality data in the United States of America. The Reproduction number is found to be 2.71914.


title: The Clinical and Economic Value of a Successful Shutdown During the SARS-CoV-2 Pandemic in Germany

text: Background and aim: Given a potential surge of COVID-19 cases in Germany, the federal government and the federal states have ordered a shutdown of businesses and social activities. An important purpose of the shutdown is to avoid overstretching intensive care unit (ICU) capacity (flattening the curve). The aim of this study was to determine the clinical and economic value of a successful shutdown. Methods: In the base case, the study compared a successful shutdown to a worst-case scenario with no ICU capacity left to treat COVID-19 patients. To this end, a decision model was developed using, e.g., information on age-specific fatality rates, ICU outcomes, and the herd protection threshold. The value of an additional life year was borrowed from new, innovative oncological drugs, as cancer reflects a condition with a similar morbidity and mortality burden in the general population in the short-term. Results: A successful shutdown is projected to yield an average gain between 0.02 and 0.08 life years (0.3 to 1.0 months) per capita in the German population. The corresponding economic value ranges between 2147 and 8056 euros per capita or, extrapolated to the total population, 5% to 19% of the gross domestic product in 2019. Nevertheless, if herd immunity is achieved through natural infection, even a shutdown that is successful in flattening the curve is expected to yield a loss of 0.40 life years per capita compared to the situation before the pandemic. Conclusion: A successful shutdown is forecasted to yield a considerable gain in life years in the German population. Nevertheless, questions around the affordability and underfunding of other parts of the healthcare system emerge.


title: CoVID-19 in Japan: What could happen in the future?

text: COVID-19 has been impacting on the whole world critically and constantly Since December 2019. We have independently developed a novel statistical time delay dynamic model on the basis of the distribution models from CCDC. Based only on the numbers of confirmed cases in different regions in China, the model can clearly reveal that the containment of the epidemic highly depends on early and effective isolation. We apply the model on the epidemic in Japan and conclude that there could be a rapid outbreak in Japan if no effective quarantine measures are carried out immediately.


SARS-CoV-2 and the Use of Chloroquine as an Antiviral Treatment


Over the Rainbow: Navigating the COVID-19 Pandemic While Living With PTSD


title: On the Relevance of Global Value Chains and the Intra-european Division of Labour

text: This article first introduces the concept, the rationale, the causes and the genesis of global value chains from a worldwide perspective in the form of a brief overview In the second empirical section, a closer look is taken at the intermediate trade integration in the EU In particular, the employment effects of the intermediate trade connections for each EU member state and for selected sectors are highlighted In the concluding section, it is explained why global value chains are particularly susceptible to rising protectionism Moreover, tentative implications of the current coronavirus pandemic are pointed out


title: HTCC as a highly effective polymeric inhibitor of SARS-CoV-2 and MERS-CoV

text: The beginning of 2020 brought us information about the novel coronavirus emerging in China. Rapid research resulted in the characterization of the pathogen, which appeared to be a member of the SARS-like cluster, commonly seen in bats. Despite the global and local efforts, the virus escaped the healthcare measures and rapidly spread in China and later globally, officially causing a pandemic and global crisis in March 2020. At present, different scenarios are being written to contain the virus, but the development of novel anticoronavirals for all highly pathogenic coronaviruses remains the major challenge. Here, we describe the antiviral activity of previously developed by us HTCC compound (N-(2-hydroxypropyl)-3-trimethylammonium chitosan chloride), which may be used as potential inhibitor of currently circulating highly pathogenic coronaviruses – SARS-CoV-2 and MERS-CoV.


title: Thoughts on Higher Medical Education Under Major Public Health Emergencies: Thinking Ahead After COVID-19 Outbreak

text: Objective: To explore the most suitable teaching and learning pattern in medical school during COVID-19 Outbreak. Design: This study is a case-control study. We had tried to apply a new blended teaching model based on 5G network that combined team-based learning (TBL) and online interaction to the students before the outbreak and then universities responded to the COVID-19 outbreak by closing campuses and shifting to other forms of distance learning. In other word, the courses started using blended teaching model before COVID-19 outbreak and might last using other forms of distance learning throughout the pandemic. Five Point Likert Scale Questionnaires which contains 20 items were used, and the effect of the two kinds of teaching patterns was compared by evaluating the indicators of core competencies of students including professionalism, attitude towards learning, knowledge and learning skills, teamwork skills, motivation in learning, adaptability and acceptance of the courses and network environment. Setting: Our study based on a single center. Participants: Fifty fourth-year medical students receiving the 5+3 pattern courses regarding internal medicine were enrolled in the study. Exposure(s) :The teaching and learning patter started using blended teaching model before COVID-19 outbreak and might last using other forms of distance learning throughout the pandemic. Main Outcome: According to the descriptive statistical analysis of the first part of the questionnaire (question 1-16), the average score of adaptability and acceptance of the courses is 2.60 lower than 3, indicating that students are more adapted to other forms of distance learning during COVID-19 outbreak; the average score of the rest of the questions is higher than 3, indicating that blended teaching model based on 5G network is superior to other forms of distance learning. The number of male students who are inclined to the blended teaching model based on 5G network is 0.13 times as much as that of female students (95%CI:0.028~0.602, p=0.009). Results: Online forms of distance learning were accepted by the students. Female students had higher expectations on the course and were more likely to adapt well to the change during the COVID-19 outbreak. However, all students preferred the blended teaching model based on 5G network that combined team-based learning (TBL) and online interaction before the pandemic. Conclusion: It indicates that medical education based on 5G network that combined team-based learning (TBL) and online interaction is a more suitable option to teach medical students online. China's experience in online higher medical education may serve as a reference to other countries during the pandemic.


title: The cross-sectional study of hospitalized coronavirus disease 2019 patients in Xiangyang, Hubei province

text: Summary Objective To describe the epidemiological and clinical characteristics of the Coronavirus Disease 2019 (COVID-19) hospitalized patients and to offer suggestions to the urgent needs of COVID-19 prevention, diagnosis and treatment. Methods We included 102 confirmed COVID-19 cases hospitalized in Xiangyang No.1 peoples hospital, Hubei, China until Feb 9th, 2020. Demographic data, laboratory findings and chest computed tomographic (CT) images were obtained and analyzed. Findings All cases were confirmed by real-time RT-PCR, including 52 males and 50 females with a mean age of 50.38 years (SD 16.86). Incubation time ranged from one to twenty days with a mean period of 8.09 days (SD 4.99). Fever (86[84.3%] of 102 patients), cough (58[57%]), fatigue (28[27%]), shortness of breath (24[23%]), diarrhea (15[15%]), expectoration (13[12%]), inappetence (11[10%]) were common clinical manifestations. We observed a decreased blood leukocyte count and lymphopenia in 21 (20.6%) and 56 (54.9%) patients, respectively. There were 66 (68%) of 97 patients with elevated C-reactive protein levels and 49 (57.6%) of 85 with increased erythrocytes sedimentation rate. Higher levels of procalcitonin and ferritin were observed in 19 (25.3%) of 75 and 12 (92.3%) of 13 patients, respectively. Eight patients were admitted to intensive care unit (ICU), six developed respiratory failure, three had multiple organ failure and three died. The cumulative positivity rate over three rounds of real-time RT-PCR was 96%. One-hundred patients were found with typical radiological abnormalities in two rounds of chest CT scans, indicating a 98% consistency with real-time RT-PCR results. Interpretation Most COVID-19 patients in Xiangyang were secondary cases without sex difference, and the rate of severe cases and death was low. Middle-to-old-age individuals were more susceptible to the virus infection and the subsequent development of severe/fatal consequences. The average incubation period was longer among our patients. We recommend prolonging the quarantine period to three weeks. Three times real-time RT-PCR plus two times CT scans is a practical clinical diagnosis strategy at present and should be used to increase the accuracy of diagnosis, thereby controlling the source of infection more effectively. Key Words SARS-CoV-2; COVID-19; epidemiological and clinical features; diagnosis


title: Classical drug digitoxin inhibits influenza cytokine storm, with implications for COVID-19 therapy

text: Influenza viruses, corona viruses and related pneumotropic viruses cause sickness and death partly by inducing a hyper-proinflammatory response by immune cells and cytokines in the host airway. Here we show that the cardiac glycoside digitoxin suppresses this response induced by influenza virus strain A/Wuhan/H3N2/359/95 in the cotton rat lung. The cytokines TNFα, GRO/KC, MIP2, MCP1, TGFβ, and IFNγ. are significantly and differentially reduced. Since the hyper-proinflammatory expression of cytokines is a host response, we suggest that digitoxin may have therapeutic potential for not only influenza and but also for coronavirus infections.


title: WisdomNet: Prognosis of COVID-19 with Slender Prospect of False Negative Cases and Vaticinating the Probability of Maturation to ARDS using Posteroanterior Chest X-Rays

text: Coronavirus is a large virus family consisting of diverse viruses, some of which disseminate among mammals and others cause sickness among humans COVID-19 is highly contagious and is rapidly spreading, rendering its early diagnosis of preeminent status Researchers, medical specialists and organizations all over the globe have been working tirelessly to combat this virus and help in its containment In this paper, a novel neural network called WisdomNet has been proposed, for the diagnosis of COVID-19 using chest X-rays The WisdomNet uses the concept of 'Wisdom of Crowds' as its founding idea It is a two-layered convolutional Neural Network (CNN), which takes chest x-ray images as input Both layers of the proposed neural network consist of a number of neural networks each The dataset used for this study consists of chest x-ray images of COVID-19 positive patients, compiled and shared by Dr Cohen on GitHub, and the chest x-ray images of healthy lungs and lungs affected by viral and bacterial pneumonia were obtained from Kaggle The network not only pinpoints the presence of COVID-19, but also gives the probability of the disease maturing into Acute Respiratory Distress Syndrome (ARDS) Thus, predicting the progression of the disease in the COVID-19 positive patients The network also slender the occurrences of false negative cases by employing a high threshold value, thus aids in curbing the spread of the disease and gives an accuracy of 100% for successfully predicting COVID-19 among the chest x-rays of patients affected with COVID-19, bacterial and viral pneumonia


title: “ARDS and Cytokine Storm in SARS-CoV-2 Infected Caribbean Vervets”

text: SARS-CoV-2 induces a wide range of disease severity ranging from asymptomatic infection, to a life-threating illness, particularly in the elderly and persons with comorbid conditions. Up to now, SARS-CoV-2 has infected more than five million and led to more than 300,000 deaths worldwide. Among those persons with serious COVID-19 disease, acute respiratory distress syndrome (ARDS) is a common and often fatal presentation. SARS-CoV-2-induced ARDS is difficult to treat clinically, and new therapeutic strategies are needed. In order to evaluate such therapeutic strategies, animal models of SARS-CoV-2 infection that manifest severe disease are needed. Here we report fatal ARDS in two African green monkeys (AGMs) infected with SARS-CoV-2 that demonstrated pathological lesions and disease similar to severe COVID-19 in humans. Moreover, we report the observation of cytokine release (cytokine storm) in three of four infected AGMs. All four animals showed increased levels of IL-6 in plasma, a predictive marker and presumptive therapeutic target in humans infected with SARS-CoV-2 infection. Our results suggest the AGM is a useful model to study disease pathogenesis of SARS-CoV-2, and for the evaluation of therapeutic interventions designed to combat serious pulmonary disease associated with this infection.


title: Association between epidemic dynamics of Covid-19 infection and ABO blood group types

text: Background: Covid-19 pandemic is the most critical challenge nowadays for the manhood, and the infection and death cases are still speedily increasing. Since there are no available vaccine and specifically effective treatment, to break the infectious way of the pandemic remains the unique measure to efficiently combat Covid-19 infection. Understanding factors that affect the Covid-19 infection can help make better balance between activity restriction and infection dynamics. This study sought to investigate association between Covid-19 infection and blood type distribution. Methods: The big data provided by World Health Organization and Johns Hopkins University were taken to assess epidemic dynamics of Covid-19 infection. Growth rate and doubling time of infection and death cases, reproductive number, infection and death cases in the mid-exponential phase were analyzed in relation to blood type distribution. Results: Growth rate of infection and death cases correlated significantly to blood type A proportion of the population positively while to blood type B proportion negatively. In comparison with lower blood type A population (< 30%) people with higher blood type A ([≥] 30%) had more infection and death cases in the early exponential phase, higher growth rates, and shorter case doubling time for infection and death. Discussion: Covid-19 infection is significantly associated with blood type distribution and people with blood type A are more susceptible to Covid-19 infection and have higher epidemic dynamics and higher case fatality rate. The results of this study provide important and useful information for fighting Covid-19 pandemic.


title: Emergence of evidence during disease outbreaks: lessons learnt from the Zika virus outbreak

text: Introduction: Outbreaks of infectious diseases trigger an increase in scientific research and output. Early in outbreaks, evidence is scarce, but it accumulates rapidly. We are continuously facing new disease outbreaks, including the new coronavirus (SARS-nCoV-2) in December 2019.The objective of this study was to describe the accumulation of evidence during the 2013-2016 Zika virus (ZIKV) outbreak in the Pacific and the Americas related to aetiological causal questions about congenital abnormalities and Guillain-Barre syndrome. Methods: We hypothesised that the temporal sequence would follow a pre-specified order, according to study design. We assessed 1) how long it takes before findings from a specific study design appear, 2) how publication of preprints could reduce the time to publication and 3) how time to publication evolves over time. Results: We included 346 publications published between March 6, 2014 and January 1, 2019. In the 2013-2016 ZIKV outbreak, case reports, case series and basic research studies were published first. Case-control and cohort studies appeared between 400-700 days after ZIKV was first detected in the region of the study origin. Delay due to the publication process were lowest at the beginning of the outbreak. Only 4.6% of the publications was available as preprints. Discussion: The accumulation of evidence over time in new causal problems generally followed a hierarchy. Preprints reduced the delay to initial publication. Our methods can be applied to new emerging infectious diseases.


title: Impaired type I interferon activity and exacerbated inflammatory responses in severe Covid-19 patients

text: Background: Coronavirus disease 2019 (Covid-19) is a major global threat that has already caused more than 100,000 deaths worldwide. It is characterized by distinct patterns of disease progression implying a diverse host immune response. However, the immunological features and molecular mechanisms involved in Covid-19 severity remain so far poorly known. Methods: We performed an integrated immune analysis that included in-depth phenotypical profiling of immune cells, whole-blood transcriptomic and cytokine quantification on a cohort of fifty Covid19 patients with a spectrum of disease severity. All patient were tested 8 to 12 days following first symptoms and in absence of anti-inflammatory therapy. Results: A unique phenotype in severe and critically ill patients was identified. It consists in a profoundly impaired interferon (IFN) type I response characterized by a low interferon production and activity, with consequent downregulation of interferon-stimulated genes. This was associated with a persistent blood virus load and an exacerbated inflammatory response that was partially driven by the transcriptional factor NFκB. It was also characterized by increased tumor necrosis factor (TNF)-α and interleukin (IL)-6 production and signaling as well as increased innate immune chemokines. Conclusion: We propose that type-I IFN deficiency in the blood is a hallmark of severe Covid-19 and could identify and define a high-risk population. Our study provides a rationale for testing IFN administration combined with adapted anti-inflammatory therapy targeting IL-6 or TNF-α in most severe patients. These data also raise concern for utilization of drugs that interfere with the IFN pathway.


title: Comparison of SARS-CoV-2 detection in nasopharyngeal swab and saliva

text: We prospectively compared the efficacy of PCR detection of SARS-CoV-2 between paired nasopharyngeal and saliva samples in nine COVID-19 patients. SARS-CoV-2 was detected in saliva in 8 of 9 (89%) patients and in all 11 samples taken within 2 weeks after disease onset. Viral load was equivalent at earlier time points but declined in saliva than nasopharyngeal samples. PCR negativity was also concordant in all 27 saliva samples from 24 patients between nasopharyngeal and saliva samples. These results suggest that saliva is a reliable noninvasive alternative to nasopharyngeal swabs and facilitate widespread PCR testing in the face of shortages of swabs and protective equipment without posing a risk to healthcare workers.


title: Age specificity of cases and attack rate of novel coronavirus disease (COVID-19)

text: Age distribution of the cases with novel coronavirus disease (COVID-19) is rather different from that of influenza. We examined the age distribution of COVID-19 cases in Japan from January to March, 2020. Children are less likely to be diagnosed as cases, and moreover, the risk of disease given exposure among children appears to be low. Both the overall risk and the conditional risk of disease given exposure are likely to be the highest among adults aged from 50-69 years. The most plausible explanation that we believe is immune imprinting to a similar virus among adults.


title: ROBUST COVID-19-RELATED CONDITION CLASSIFICATION NETWORK

text: COVID-19 can exponentially precipitate life-threatening emergencies as witnessed during the recent spreading of a novel coronavirus infection which can rapidly evolve into lung collapse and respiratory distress (among other various severe clinical conditions). Our study evaluates the performance of a tailor-designed deep convolutional network on the tasks of early detection and localization of radiological signs associated to COVID-19 on frontal chest X-rays. We also asses the frameworks capacity in differentiating the above-mentioned signs, which are usually confused with the more usual common bacterial and viral pneumonias. Open-source chest X-ray images categorized as Normal, Non-COVID-19 and COVID-19 pneumonias were downloaded from the NIH (n=2,259), RSNA (n=600) and HM Hospitales (n=2,307). Our algorithmic framework was able to precisely detect the images with COVID19- related radiological findings (mean Accuracy: 90.5%; Sensitivity: 80.6%; Specificity: 98.0%), whilst correctly categorizing images deemed as Non-COVID-19 pneumonias (mean Accuracy: 88.4%; Sensitivity: 93.3%; Specificity: 92.0%) and normal chest X- rays (mean Accuracy 92.1%; Sensitivity: 91.8%; Specificity: 94.3%). The associated results show that our AI framework is able to classify COVID-19 accurately, making of it a potential tool to improve the diagnostic performance across primary-care centres and, to grant priority to a subset of algorithmic selected images for urgent follow-on expert review. This would sensibly accelerate diagnosis in remote locations, reduce the bottleneck on specialized centres, and/or help to alleviate the needs on situations of scarcity in the availability of molecular tests.


title: Epidemiological monitoring and control perspectives: application of a parsimonious modelling framework to the COVID-19 dynamics in France

text: SARS-Cov-2 virus has spread over the world creating one of the fastest pandemics ever. The absence of immunity, asymptomatic transmission, and the relatively high level of virulence of the COVID-19 infection it causes led to a massive flow of patients in intensive care units (ICU). This unprecedented situation calls for rapid and accurate mathematical models to best inform public health policies. We develop an original parsimonious model that accounts for the effect of the age of infection on the natural history of the disease. Analysing the ongoing COVID-19 in France, we estimate the value of the key epidemiological parameters, such as the basic reproduction number (R0), and the efficiency of the national control strategy. We then use our deterministic model to explore several scenarios posterior to lock-down lifting and compare the efficiency of non pharmaceutical interventions (NPI) described in the literature.


title: Managing Migraine in the Times of COVID-19 Pandemic

text: COVID-19 pandemic is an emerging, rapidly evolving situation. Migraine is one of the commonest and highly disabling chronic neurological diseases in the world. During the pandemic and lockdown, migraine patients are facing an enormous problem in getting optimum care because of difficulty in access, forced social isolation, and encountering a health system that is getting rapidly overwhelmed. It is important that they must be protected by minimizing their visits to the clinics and emergency departments. Paradoxically multiple triggers are in operation which is likely to increase their headache frequency. Hence physicians should be made aware of the new rules of the game in treating migraines during this time of the pandemic so that these patients get optimum treatment and care and don’t feel left out. This review tries to answer a series of questions related to managing migraines in the times of COVID-19 pandemic.


The ventilator solution for COVID -19 patient at rural tertiary care hospital


title: Understanding the present status and forecasting of COVID―19 in Wuhan

text: The present status of COVID―19 is analyzed and the end of the disease is forecasted. The peak of the epidemic is different in three regions, Wuhan, Hubei province except Wuhan, and mainland China except Hubei. In two regions except Wuhan, the peak of the epidemic passed ten days ago. If the trend until February 11 does not change, the disease may end by the end of February. In Wuhan, the epidemic reached a peak but the reported number of newly infected patients fluctuates largely. We need to know the reason for the big fluctuation to forecast the end of the disease.


title: Analyzing the World-Wide Impact of Public Health Interventions on the Transmission Dynamics of COVID-19

text: We analyze changes in the reproduction number, R, of COVID-19 in response to public health interventions. Our results indicate that public health measures undertaken in China reduced R from 1.5 in January to 0.4 in mid-March 2020. They also suggest, however, the limitations of isolation, quarantine, and large-scale attempts to limit travel. While the world-wide reproduction number briefly dropped below 1 as China implemented extensive public health measures, the introduction of the virus to other nations swiftly led to an increasing world-wide average value of R. In Italy, the nation hardest-hit following China, social distancing measures brought the local value of R down from 3.71 to 2.51. Nonetheless, the value of R in Italy persisted at levels well above 1, allowing for ongoing transmission. By mid-March 2020, as COVID-19 spread in areas without extensive public health interventions in place, the world-wide value of R increased to a level similar to that of late January.


title: Applying a Prospective Space-Time Scan Statistic to Examine the Evolution of COVID-19 Clusters in the State of Sao Paulo, Brazil

text: We present the first geographic study that uses space-time statistics to monitor COVID-19 in Brazil. The first cases of COVID-19 were confirmed in December 2019 in Wuhan, China, caused by the contamination of the SARS-CoV-2 virus, and quickly turned into a pandemic. In Brazil, the first case occurred on January 23rd, 2020 but was officially reported by the Brazilian Ministry of Health on February 25th. Since then, the number of deaths and people infected by COVID-19 in Brazil have been steadily increasing. Despite the underreporting of coronavirus cases by government agencies across the country, the State of Sao Paulo has the highest rate among all Brazilian States. Thus, it is essential to detect which areas contain the highest concentration of COVID-19 to implement public policies, to mitigate the spread of the epidemic. To identify these critical areas, we utilized daily confirmed case data from the Brasil.IO website between February 25th, 2020 to May 5th, 2020; which were aggregated to the municipality level. A prospective space-time scan statistic was applied to evaluate possible active clusters in three different time periods. The results visualize the space-time evolution and dynamics of COVID-19 clusters in the State of Sao Paulo. Since the first study period, the results highlight approximately 4.6 times the number of municipalities belonging to a significant cluster with a RR>1 on May 5th. These results can inform health authorities and public management to take the necessary measures to minimize the transmission of COVID-19 and track the evolution of significant space-time clusters.


title: Type I and III interferons disrupt lung epithelial repair during recovery from viral infection

text: Excessive cytokine signalling frequently exacerbates lung tissue damage during respiratory viral infection. Type I and III interferons (IFN-α/β and IFN-λ) are host-produced antiviral cytokines and currently considered as COVID-19 therapy. Prolonged IFN-α/β responses can lead to harmful proinflammatory effects, whereas IFN-λ mainly signals in epithelia, inducing localised antiviral immunity. Here we show that IFN signalling interferes with lung repair during influenza recovery, with IFN-λ driving these effects most potently. IFN-induced p53 directly reduces epithelial proliferation and differentiation, increasing disease severity and susceptibility to bacterial superinfections. Hence, excessive or prolonged IFN-production aggravates viral infection by impairing lung epithelial regeneration. Therefore, timing and duration are critical parameters of endogenous IFN action, and should be considered carefully for IFN therapeutic strategies against viral infections like influenza and COVID-19. One Sentence Summary A novel IFN-mediated mechanism of immunopathology during respiratory virus infection by interference with lung tissue repair.


title: Nonstructural proteins of Novel Coronavirus (SARS-CoV-2)

text: Abstract Coronaviruses (CoVs) are pathogens that infect a large variety of vertebrate animals, resulting in mainly respiratory and enteric diseases An epidemic of severe acute respiratory syndrome (SARS) occurred in China in 2002, and the causative agent was designated as SARS-CoV Ten years after the SARS outbreak, another highly pathogenic human CoV, designated as Middle East respiratory syndrome (MERS)-CoV, emerged in Saudi Arabia Now, we faces on an epidemic of Novel coronavirus, (SARS-CoV-2) The nonstructural protein (nsp) 1 of SARS-CoV and MERS-CoV are the most studied among CoVs and are known to inhibit host gene expression by translational shutoff and host mRNA degradation This two-pronged strategy of nsp1 inhibits expression of the IFN gene Murine models of SARS-CoV have revealed that the dysregulated type I IFN response is a key factor for inducing lethal pneumonia These accumulated data indicate that the nsp1 of CoV is a major virulence factor We speculate that the nsp1 of SARS-CoV-2 has similar function to SARS and MERS-CoV


title: Fear, affective semiosis, and management of the pandemic crisis: Covid-19 as semiotic vaccine?

text: The COVID-19 pandemic represents an extraordinary challenge to clinicians, health care institutions and policymakers. The paper outlines a psychoanalytically grounded semiotic-cultural psychological interpretation of such a scenario. First, we underline how the actual emotional reaction (mainly of fear) of our society is a marker of how the mind functions in conditions of affective activation related to heightened uncertainty: it produces global, homogenizing and generalizing embodied interpretations of reality, at the cost of more fine-grained and differentiated analytical thought. Such a process, called affective semiosis, represents an adaptive response to the emergency in the short-term. Second, we argue that this adaptive value provided by affective semiosis will be reduced when we have to deal with the process of managing the transition to the post-crisis and the governance of the medium and long-term impact of the crisis. Third, we suggest that, in order to manage the pandemic crisis on a longer temporal frame, affective semiosis has to be integrated with less generalized and more domain-specific ways of interpreting reality. To this end, semiotic capital (i.e., culturally-mediated symbolic resources) should be promoted in order to enable people to interiorize the supra-individual and collective dimension of life. Accordingly, COVID-19 is proposed as a semiotic vaccine, a disruption in our everyday life routines which has the potential of opening the way to a semiotic re-appropriation of the collective dimensions of our experience.


title: Basic principles for the management of neurological patients during the COVID-19 pandemic

text: In a COVID-19 pandemic, a neurologist needs to be able to assess the risks of virus infection in patients with individual neurological diseases. The review presents categories of risk groups from the Association of British Neurologists for neuromuscular diseases, multiple sclerosis and other autoimmune diseases of the central nervous system, stroke, epilepsy and Parkinson's disease. The risk of infection and the management of patients with neuromuscular diseases are analyzed in detail. The use of multiple sclerosis disease modifying drugs, the treatment of stroke patients are discussed. The data from the international guidelines for the management of patients with epilepsy and Parkinson's disease are presented.


title: Possible molecular and paracrine involvement underlying the pathogenesis of COVID-19 cardiovascular complications

text: Coronavirus disease 2019 (COVID-19) has been declared a pandemic on 11 March 2020 by the WHO Despite being mainly a respiratory virus, cardiac complications have been described These range from sudden cardiac death to subtle diastolic dysfunction after recovery from COVID-19 The commonest cardiac presentation to date is acute heart failure resulting from biventricular or left ventricular hypokinesis and elevation of cardiac troponins It has been shown that COVID-19 downregulates angiotensin-converting enzyme-2, which has protective effects on the endothelium and cardiomyocytes It has also been proven that COVID-19 induces a state of hypercytokinaemia, some cytokines such as interleukin-1 and interleukin-6 have an injurious effect on the myocardium and endothelium, respectively Such pathogenic mechanisms might play a crucial role in induction of cardiomyocyte injury and impaired myocardial perfusion probably through coronary endothelial dysfunction The understanding and linking of such mechanisms might help in tailoring drug repurposing for treatment or prophylaxis of COVID-19 cardiovascular complications Received 6 April 2020 Accepted 14 April 2020 Correspondence to Antoine Fakhry AbdelMassih, MD, Pediatrics’ Department, Pediatric Cardiology unit, Cairo University Children Hospital, Faculty of Medicine, Cairo University, Kasr Al Ainy Street, Cairo 12411, Egypt, E-mail: antoine abdelmassih@kasralainy edu eg © 2020Wolters Kluwer Health Lippincott Williams Wilkins


title: COVID19 REAL-WORLD DATA FOR THE US AND LESSONS TO RE-OPEN BUSINESSRevisedMEDRXIV/2020/109538

text: In March of 2020, the COVID19 pandemic had expanded to the United States of America (US). Companies designated as essential for the US had to maintain productivity in spite of the growing threat created by the SARS-CoV-2 virus. With this report, we present the response of one such company, the Lennar Corporation, a major homebuilder in the US. Within days, Lennar had implemented a morning health check via its enterprise resource planning system , to identify associates (employees) who were sick, or not in their usual state of health. With this survey, Lennar was able to ensure that no one sick would show up to work, and instead, would self-quarantine at home. Furthermore, with thorough contact tracking, associates exposed to COVID19 patients (suspected or RT-PCR test-confirmed), were also asked to self-quarantine. This survey, in addition to other safety measures, such as an overhaul of the company with nearly 50% of the company working from home, prolific communication, and many more measures, Lennar was able to function safely for its associates and successfully as an enterprise. The data that we present here are real world data collected in the context of working throughout a dreadful pandemic, and the lessons learned could be helpful to other companies that are preparing to return to work.


title: Longitudinal laboratory testing tied to PCR diagnostics in COVID-19 patients reveals temporal evolution of distinctive coagulopathy signatures

text: Temporal inference from laboratory testing results and their triangulation with clinical outcomes as described in the associated unstructured text from the provider notes in the Electronic Health Record (EHR) is integral to advancing precision medicine. Here, we studied 181 COVIDpos and 7,775 COVIDneg patients subjected to 1.3 million laboratory tests across 194 assays during a two-month observation period centered around their SARS-CoV-2 PCR testing dates. We found that compared to COVIDneg at the time of clinical presentation and diagnostic testing, COVIDpos patients tended to have higher plasma fibrinogen levels and similarly low platelet counts, with approximately 25% of patients in both cohorts showing outright thrombocytopenia. However, these measures show opposite longitudinal trends as the infection evolves, with declining fibrinogen and increasing platelet counts to levels that are lower and higher compared to the COVIDneg cohort, respectively. Our EHR augmented curation efforts suggest a minority of patients develop thromboembolic events after the PCR testing date, including rare cases with disseminated intravascular coagulopathy (DIC), with most patients lacking the platelet reductions typically observed in consumptive coagulopathies. These temporal trends present, for the first time, fine-grained resolution of COVID-19 associated coagulopathy (CAC), via a digital framework that synthesizes longitudinal lab measurements with structured medication data and neural network-powered extraction of outcomes from the unstructured EHR. This study demonstrates how a precision medicine platform can help contextualize each patients specific coagulation profile over time, towards the goal of informing better personalization of thromboprophylaxis regimen.


title: Microscopic Review of Nasopharyngeal Swabs as a Means of Benchside Quality Assurance

text: Nasopharygneal swabs (NPS) are the collection modality recommended by the Centers for Disease Control and Prevention (CDC) for reverse-transcription polymerase chain reaction (RT-PCR) testing for SARS-CoV2. NPS gather both extracellular material and human respiratory epithelial cells and, when used with RT-PCR, have reliable sensitivity for detection of viral infection. However, at our institution, we identified a 1.7% re-order rate within 7-days for NPS for respiratory pathogen RT-PCR, which we hypothesize may be due to low confidence in adequate sample collection. We sought to identify an inexpensive and accessible strategy for benchside quality assurance of NPS adequacy by observing microscopic content of viral transport media. For 801 NPS samples collected in November 2019, we air-dried and safranin-stained aliquots of viral transport media on glass slides. We then counted morphologically distinct ciliated columnar epithelial cells (CCEs). 19% of samples negative by RT-PCR for respiratory pathogens had no CCEs, while just 6% of positive samples exhibited the same. Pearson's Chi-squared test was used to compare presence of CCEs between samples that were positive and negative for respiratory pathogens by RT-PCR (p=3.3x10-38). The negative predictive value (NPV) of finding no identifiable CCEs on microscopy was 85%. We posit that samples without identifiable CCEs may have been inadequately collected. The basic, benchside protocol using inexpensive laboratory reagents that we describe here could help improve accuracy and accessibility of NPS and RT-PCR testing for SARS-CoV2 and other respiratory pathogens while conserving limited resources in the face of a pandemic.


title: COVID-19 awareness among a group of Egyptians and their perception toward the role of dentists in its prevention: a pilot cross-sectional survey

text: Aim: The main purpose of the study is to assess the awareness of a group of Egyptians about COVID-19 infection and their perception of the role of dentists in its prevention. Subjects and methods: An observational cross-sectional survey included 74 participants who attended Minia University Dental Hospital, Minia City, Egypt, from 10 March to 2 April 2020. A face-to-face interview using an anonymous questionnaire was carried out in this study. The questionnaire contained 20 questions divided into three parts; the first part included the participants’ baseline characteristics. The second part analyzed the participants' awareness of COVID-19 infection through ten questions. Finally, four questions outlined participants' perception of the role of dentists in preventing the spread of COVID-19. Results: Overall participant awareness was adequate at 55.4%. The percentages of “good” and “poor” overall awareness scores were 40.5% and 4.1%, respectively. Most respondents' perception of dentists' role in COVID-19 prevention was poor. All baseline characteristics showed no statistically significant difference related to the participants' awareness about COVID-19 infection and its spread (p > 0.05). Conclusion: From the findings of the present pilot study, it can be concluded that the general population's awareness of COVID-19 infection and its route of transmission was adequate. Participants' understanding of the role of dentists in COVID-19 prevention was poor.


title: Angiotensin-converting enzyme 2, a SARS-CoV-2 receptor, is upregulated by interleukin-6 via STAT3 signaling in rheumatoid synovium

text: Detected in December 2019, the coronavirus disease 2019 (COVID-19) has since spread all over the world, resulting in a global pandemic. The disease is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), and its symptoms usually include cough, fever, and gastrointestinal problems. Although the prevalence of rheumatoid arthritis (RA) is about 1 % of the global population and RA patients naturally have a chance of acquiring COVID-19 in this pandemic, no studies have considered the expression of angiotensin-converting enzyme 2 (ACE2) (a receptor for SARS-CoV-2) in synovial tissues. Our presenting data revealed that ACE2 expression was elevated in active rheumatoid synovium, and siRNA against STAT3 was able to downregulate ACE2 expression, which was in turn induced by IL-6 signaling.


A blank piece of paper


title: Are They Just Two Children COVID-19 Cases Confused With Flu?

text: COVID-19, an emerging infectious disease, has quickly spread all over the world. All human populations are susceptible to this disease. Here we present two pediatric COVID-19 cases, both of whom exhibited negative SARS-CoV-2 nucleic acid tests upon nasopharyngeal swab and were initially diagnosed with influenza A infection. COVID-19 was later confirmed in both patients by serum antibodies of SARS-CoV-2 and nucleic acid test on stool samples. Because children are susceptible to many respiratory pathogens, especially influenza, we concluded that children can be coinfected with multiple pathogens, and more attention should be paid to the exploration of SARS-CoV-2 during the pandemic of COVID-19. This report shows the possibility of misdiagnosis or missed diagnosis of children with COVID-19. We suggest that highly suspected pediatric COVID-19 cases with negative nucleic acid tests on nasopharyngeal swabs should be further checked by performing a nucleic acid test on stool samples and testing serum for antibodies against SARS-CoV-2.


title: Decline in Emergent and Urgent Care during the COVID-19 Pandemic

text: Due to the ongoing coronavirus disease (COVID-19) pandemic, there are concerns that patients may be avoiding care for emergent and urgent health conditions due to fear of contagion or as an unintentional consequence of government orders to postpone non-essential services. We therefore sought to evaluate the effect of the COVID-19 pandemic on the number of patient encounters for select emergent or urgent diagnoses at a large tertiary-care academic medical center in Boston. Inpatient diagnoses included acute myocardial infarction (MI) and stroke, and outpatient but urgent diagnoses included new referrals for breast and hematologic malignancies. For each condition, we used a difference-in-differences approach to estimate the proportional change in number of encounters during the pandemic (March-April 2020) compared with earlier in the same year (January-February 2020), using equivalent periods in 2019 as a control. After the onset of the pandemic, we observed significant reductions in hospitalizations for MI (difference-in-differences estimate, 0.67; 95%CI, 0.46-0.96; P=0.04) and stroke (difference-in-differences estimate, 0.42; 95%CI, 0.28-0.65; P<0.001) (Table). In the ambulatory setting, there was a reduction in referrals for breast cancer and hematologic cancers, but this did not reach statistical significance until the month after the onset of the pandemic. Our findings suggest an urgent need for public health messaging to ensure that patients continue to seek care for acute emergencies. In addition, decisions by health systems regarding when to reinitiate non-emergent care should carefully factor in the harms of delayed diagnosis and treatment occurring during the COVID-19 pandemic.


title: Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2

text: SARS-CoV-2 is the causative agent of the current COVID-19 pandemic. A major virulence factor of SARS-CoVs is the nonstructural protein 1 (Nsp1) which suppresses host gene expression by ribosome association via an unknown mechanism. Here, we show that Nsp1 from SARS-CoV-2 binds to 40S and 80S ribosomes, resulting in shutdown of capped mRNA translation both in vitro and in cells. Structural analysis by cryo-electron microscopy (cryo-EM) of in vitro reconstituted Nsp1-40S and of native human Nsp1-ribosome complexes revealed that the Nsp1 C-terminus binds to and obstructs the mRNA entry tunnel. Thereby, Nsp1 effectively blocks RIG-I-dependent innate immune responses that would otherwise facilitate clearance of the infection. Thus, the structural characterization of the inhibitory mechanism of Nsp1 may aid structure-based drug design against SARS-CoV-2.


title: A streamlined approach to rapidly detect SARS-CoV-2 infection, avoiding RNA extraction

text: In the current pandemic, the presence of SARS-CoV-2 RNA in samples by nucleic acid (NA) molecular analysis is the only method available to diagnose COVID-19 disease and to assess patients' infectiveness. Recently, the demand for laboratory reagents has greatly increased; in particular, there is a worldwide shortage of RNA extraction kits. Here, we describe a fast, simple and inexpensive method for the detection of SARS CoV-2 RNA, which includes a pretreatment with Proteinase K and a heating-cooling cycle before the amplification. This method bypasses the RNA extraction step; it leads to a higher amount of available viral RNA compared to the automated extraction methods, and generates the same profile in the subsequent amplification phase.


title: Site-specific N-glycosylation Characterization of Recombinant SARS-CoV-2 Spike Proteins

text: The glycoprotein spike (S) on the surface of SARS-CoV-2 is a determinant for viral invasion and host immune response. Herein, we characterized the site-specific N-glycosylation of S protein at the level of intact glycopeptides. All 22 potential N-glycosites were identified in the S-protein protomer and were found to be preserved among the 753 SARS-CoV-2 genome sequences. The glycosites exhibited glycoform heterogeneity as expected for a human cell-expressed protein subunits. We identified masses that correspond to 157 N-glycans, primarily of the complex type. In contrast, the insect cell-expressed S protein contained 38 N-glycans, primarily of the high-mannose type. Our results revealed that the glycan types were highly determined by the differential processing of N-glycans among human and insect cells. This N-glycosylation landscape and the differential N-glycan patterns among distinct host cells are expected to shed light on the infection mechanism and present a positive view for the development of vaccines and targeted drugs.


title: Multidisciplinary team management and cesarean delivery for a Jordanian woman infected with SARS-COV-2: A case report

text: The SARS-COV-2 virus appears to have originated in Hubei Province in China towards the end of 2019 and has spread worldwide. Currently, there is little literature on COVID-19, and even less on its effect on pregnant mothers and infants. At this time, there are no clear recommendations specific to pregnant women with COVID-19. We report the multidisciplinary team management of a cesarean delivery for a woman infected with SARS-COV-2, including her pre-delivery care, intraoperative considerations, and post-delivery recommendations for the mother and baby. We also discuss the currently available recommendations and guidelines on the management of such cases.


title: SARS-CoV-2 induces activation and diversification of human plasmacytoid pre-dendritic cells

text: Several studies have analyzed antiviral immune pathways in severe COVID-19 patients. However, the initial steps of antiviral immunity are not known. Here, we have studied the interaction of isolated primary SARS-CoV-2 viral strains with human plasmacytoid pre-dendritic cells (pDC), a key player in antiviral immunity. We show that pDC are not permissive to SARS-CoV-2 infection. However, they efficiently diversified into activated P1-, P2-, and P3-pDC effector subsets in response to viral stimulation. They expressed checkpoint molecules at levels similar to influenza virus-induced activation. They rapidly produced high levels of interferon-α, interferon-λ1, IL-6, IP-10, and IL-8. Importantly, all major aspects of SARS-CoV-2-induced pDC activation were inhibited by hydroxychloroquine, including P2- and P3-pDC differentiation, the expression of maturation markers, and the production of interferon-α and inflammatory cytokines. Our results indicate that pDC may represent a major player in the first line of defense against SARS-CoV-2 infection, and call for caution in the use of hydroxychloroquine in the early treatment of the disease.


title: Assessing the impact of a symptom-based mass screening and testing intervention during a novel infectious disease outbreak: The case of COVID-19

text: A symptom-based mass screening and testing intervention (MSTI) can identify a large fraction of infected individuals during an infectious disease outbreak. China is currently using this strategy for the COVID-19 outbreak. However, MSTI might lead to increased transmission if not properly implemented. We investigate under which conditions MSTI is beneficial.


title: Better Strategies for Containing COVID-19 Epidemics --- A Study of 25 Countries via an Extended Varying Coefficient SEIR Model

text: We evaluate the effectiveness of COVID-19 control strategies of 25 countries which have endured more than four weeks of community infections. With an extended SEIR model that allows infections in both the exposed and infected states, the key epidemic parameters are estimated from each country's data, which facilitate the evaluation and cross-country comparison. It is found quicker control measures significantly reduce the average reproduction numbers and shorten the time length to infection peaks. If the swift control measures of Korea and China were implemented, average reductions of 88% in the confirmed cases and 80% in deaths would had been attained for the other 23 countries from start to April 10. Effects of earlier or delayed interventions in the US and the UK are experimented which show at least 75% (29%) less infections and deaths can be attained for the US (the UK) under a Five-Day Earlier experiment. The impacts of two removal regimes (Korea and Italy) on the total infection and death tolls on the other countries are compared with the naturally forecast ones, which suggest there are still ample opportunity for countries to reduce the final death numbers by improving the removal process.


title: The correspondence between the structure of the terrestrial mobility network and the emergence of COVID-19 in Brazil

text: The inter-cities mobility network is of great importance in understanding outbreaks, especially in Brazil, a continental-dimension country. Grounded on the complex networks approach, cities are here represented as nodes and the flows as weighted edges - these geographical graphs, (geo)graphs, are handled in a Geographical Information System. We adopt the IBGE database from 2016, which contains the weekly flow of people between cities in terrestrial vehicles. The present work aims to investigate the correspondences of the networks' measures, like strength, degree, and betweenness with the emergence of cities with confirmed cases of COVID-19 in Brazil, and special attention is given to the state of Sao Paulo. We show that the results are better when certain thresholds are applied to the networks' flows to neglect the lowest-frequency travels. The correspondences presented statistical significance for most measures up to a certain period. Until the end of April, the best matchings are with the strength measure (total flow related to a node/city) under a high flow threshold in the Sao Paulo state, when the most connected cities are reached. After this stage, the lower thresholds become more suitable, indicating a possible signature of the outbreak interiorization process. Surprisingly, some countryside cities such as Campina Grande (state of Paraiba), Feira de Santana (state of Bahia), and Caruaru (state of Pernambuco) have higher strengths than some states' capitals. Furthermore, some cities from the Sao Paulo state such as Presidente Prudente and Ribeirao Preto are captured in the top-rank positions of all the analyzed network measures under different flow thresholds. Their importance in mobility is crucial and they are potential super spreaders like the states' capitals. Our analysis offers additional tools for understanding and decision support to inter-cities mobility interventions regarding the SARS-CoV-2 and other epidemics.


Rethinking COVID-19 ‘pneumonia’ – is this primarily a vaso-occlusive disease, and can early anticoagulation save the ventilator famine?


title: The Role of Chest Computed Tomography in Asymptomatic Patients of Positive Coronavirus Disease 2019: A Case and Literature Review

text: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an ongoing global health emergency. At present, patients are the primary source of infection. A randomly diagnosed confirmed case of COVID-19 highlights the importance of computerized tomography of thorax in diagnosing asymptomatic patients. In the early phase of COVID-19, routine screenings miss patients who are virus carriers, and tracking travel history is of paramount importance to early detection and isolation of SARS-CoV-2 cases.


title: COVID-19 attack rate increases with city size

text: The current outbreak of novel coronavirus disease 2019 (COVID-19) poses an unprecedented global health and economic threat to interconnected human societies. Until a vaccine is developed, strategies for controlling the outbreak rely on aggressive social distancing. These measures largely disconnect the social network fabric of human societies, especially in urban areas. Here, we estimate the growth rates and reproductive numbers of COVID-19 in US cities from March 14th through March 19th to reveal a power-law scaling relationship to city population size. This means that COVID-19 is spreading faster on average in larger cities with the additional implication that, in an uncontrolled outbreak, larger fractions of the population are expected to become infected in more populous urban areas. We discuss the implications of these observations for controlling the COVID-19 outbreak, emphasizing the need to implement more aggressive distancing policies in larger cities while also preserving socioeconomic activity.


title: Systemic and mucosal antibody secretion specific to SARS-CoV-2 during mild versus severe COVID-19

text: Background Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes an acute illness termed coronavirus disease 2019 (COVID-19). Humoral immune responses likely play an important role in containing SARS-CoV-2, however, the determinants of SARS-CoV-2-specific antibody responses are unclear. Methods Using immunoassays specific for the SARS-CoV-2 spike protein, we determined SARS-CoV-2-specific immunoglobulin A (IgA) and immunoglobulin G (IgG) in sera and mucosal fluids of two cohorts, including patients with quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR)-confirmed SARS-CoV-2 infection (n = 56; median age 61 years) with mild versus severe COVID-19, and SARS-CoV-2-exposed healthcare workers (n = 109; median age 36 years) with or without symptoms and tested negative or positive by RT-qPCR. Findings On average, SARS-CoV-2-specific serum IgA titers in mild COVID-19 cases became positive eight days after symptom onset and were often transient, whereas serum IgG levels remained negative or reached positive values 9–10 days after symptom onset. Conversely, patients with severe COVID-19 showed a highly significant increase of SARS-CoV-2-specific serum IgA and IgG titers as a function of duration since symptom onset, independent of patient age and comorbidities. Very high levels of SARS-CoV-2-specific serum IgA correlated with severe acute respiratory distress syndrome (ARDS). Interestingly, some of the SARS-CoV-2-exposed healthcare workers with negative SARS-CoV-2-specific IgA and IgG serum titers had detectable SARS-CoV-2-specific IgA antibodies in their nasal fluids and tears. Moreover, SARS-CoV-2-specific IgA levels in nasal fluids of these healthcare workers were inversely correlated with patient age. Interpretation These data show that systemic IgA and IgG production against SARS-CoV-2 develops mainly in severe COVID-19, with very high IgA levels seen in patients with severe ARDS, whereas mild disease may be associated with transient serum titers of SARS-CoV-2-specific antibodies but stimulate mucosal SARS-CoV-2-specific IgA secretion. The findings suggest four grades of antibody responses dependent on COVID-19 severity.


title: Detecting first layer bond quality during FDM 3D printing using a discrete wavelet energy approach

text: Abstract Fused Deposition Modeling (FDM) is a highly versatile additive manufacturing method for 3D printing thermoplastic-based components at small as well as larger production scales. By combining the filament with fibers from other materials including wood, metal, glass, and carbon, the method can easily be adapted to print complex parts using a variety of materials. However, despite its popularity, online print quality and machine monitoring continue to remain a challenge. Here, we present the preliminary results from our efforts on using cheap off-the-shelf sensors in combination with discrete wavelet transform analysis to identify the differences in the vibroacoustic signals measured near the print area during successful and failed first layer filament deposition on the build plate. A failure in creating a strong first layer bond between the extruded filament and the build plate always results in a print failure and is one of most common print issues occurring in FDM printing. By controlling the extruder and build plate temperatures, we control the filament – build plate bond strength while measuring the generated vibroacoustic signals using a PVDF piezo sensor. The measured signals are analyzed using a discrete wavelet transform to partition the signal energy into different energy levels. For the cases studied, we find that the relevant noticeable differences can be observed in specific energy levels during good and bad bond formation. Reconstructing the signal using these energy contributions provides a time domain representation of signal differences under different conditions. The obtained results demonstrate that a cheap and easy to implement method can be developed using PVDF sensors in combination with a wavelet-based signal analysis approach.


title: Epidemiologic character of COVID-19 in Kazakhstan: A preliminary report

text: OBJECTIVE: Coronavirus Disease 2019 (COVID-19), named the etiological agent of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has recently emerged in Wuhan City, Hubei Province, China, in December 2019. Kazakhstan’s border proximity to China has led to preventive measures in the country since January. This study aims to evaluate the epidemiologic characters of the first recorded cases in Kazakhstan. METHODS: Here, we reviewed the preparedness of the infection control and prevention procedures in Kazakhstan and evaluated the epidemiological characters of confirmed cases in Kazakhstan. The data for COVID-19 cases recorded from March 13 to April 6, 2020, were obtained from the Sanitary Epidemiological Service. Age, gender and their living place were recorded. The severity of infection, geographical distribution, gender and age group of cases were analyzed. RESULTS: Four phases of preventive measures used in respiratory infections have been implemented in Kazakhstan since January 6, 2020. The first case was recorded on March 13. During the period of March 13 and April 06, 629 cases with COVID-19 were recorded in Kazakhstan. Of these, 45 patients recovered, six had resulted in death; 535 (85%) of cases were mild and/or asymptomatic, 72 (11.5%) - moderate, 22 (3.5%) - severe. Of these, 7.5% of the cases were registered as children and course was mild. CONCLUSION: The cases are increasing in Kazakhstan as seen in other countries. Currently, the strict implication of respiratory infection control measurement in public and health care services are still very important.


Lessons learned from SARS-CoV and MERS-CoV: FDA-approved Abelson tyrosine-protein kinase 2 inhibitors may help us combat SARS-CoV-2


title: If long-term suppression is not possible, how do we minimize mortality for COVID-19 and other emerging infectious disease outbreaks?

text: If COVID-19 containment policies fail and social distancing measures cannot be sustained until vaccines becomes available, the next best approach is to use interventions that reduce mortality and prevent excess infections while allowing low-risk individuals to acquire immunity through natural infection until population level immunity is achieved. In such a situation, allowing some infections to occur in lower-risk groups might lead to an overall greater reduction in mortality than trying to protect everyone equally.


title: Antimicrobial mouthwashes (gargling) and nasal sprays to protect healthcare workers when undertaking aerosol-generating procedures (AGPs) on patients without suspected or confirmed COVID-19 infection

text: Objectives: This is a protocol for a Cochrane Review (intervention) The objectives are as follows: To assess the benefits and harms of antimicrobial mouthwashes and nasal sprays administered to healthcare workers (HCWs) and/or patients when undertaking aerosol-generating procedures (AGPs) on patients without suspected or confirmed COVID-19 infection


title: An ounce of public health for COVID-19?

text: Multifaceted nonpharmaceutical interventions supported by data restricted spread of COVID-19 in China


title: Prevalence and Predictors of General Psychiatric Disorders and Loneliness during COVID-19 in the United Kingdom: Results from the Understanding Society UKHLS

text: Despite ample research on the prevalence of specific psychiatric disorders during COVID-19, we know little about how the pandemic affects the general wellbeing of a wider population. The study investigates the prevalence and predictors of general psychiatric disorders measured by the 12-item General Health Questionnaire (GHQ-12) and frequency of loneliness during COVID-19 in the United Kingdom, a country heavily hit by the pandemic. We analyzed 15,530 respondents of the first large-scale, nationally representative survey of COVID-19 in a developed country, the first wave of Understanding Society COVID-19 Study. Results show that 29.2% of the respondents score 4 or more, the caseness threshold, on the general psychiatric disorder measure, and 35.86% of the respondents sometimes or often feel lonely. Regression analyses show that those who have or had COVID-19-related symptoms are more likely to develop general psychiatric disorders and are lonelier. Women and people in their 30s have higher risks of general psychiatric disorders and loneliness, while having a job and living with a partner are protective factors. This study showcases the general psychiatric disorders and loneliness of broader members of the society during COVID-19 and the underlying social disparities.


title: In Silico Trial to test COVID-19 candidate vaccines: a case study with UISS platform

text: SARS-CoV-2 is a severe respiratory infection that infects humans. Its outburst entitled it as a pandemic emergence. To get a grip on this outbreak, specific preventive and therapeutic interventions are urgently needed. It must be said that, until now, there are no existing vaccines for coronaviruses. To promptly and rapidly respond to pandemic events, the application of in silico trials can be used for designing and testing medicines against SARS-CoV-2 and speed-up the vaccine discovery pipeline, predicting any therapeutic failure and minimizing undesired effects. Here, we present an in silico platform that showed to be in very good agreement with the latest literature in predicting SARS-CoV-2 dynamics and related immune system host response. Moreover, it has been used to predict the outcome of one of the latest suggested approach to design an effective vaccine, based on monoclonal antibody. Universal Immune System Simulator (UISS) in silico platform is potentially ready to be used as an in silico trial platform to predict the outcome of vaccination strategy against SARS-CoV-2.


title: Rate Estimation and Identification of COVID-19 Infections: Towards Rational Policy Making During Early and Late Stages of Epidemics

text: Pandemics have a profound impact on our world, causing loss of life, affecting our culture and historically shaping our genetics. The response to a pandemic requires both resilience and imagination. It has been clearly documented that obtaining an accurate estimate and trends of the actual infection rate and mortality risk are very important for policy makers and medical professionals. One cannot estimate mortality rates without an accurate assessment of the number of infected individuals in the population. This need is also aligned with identifying the infected individuals so they can be properly treated, monitored and tracked. However, accurate estimation of the infection rate, locally, geographically and nationally is important independently. These infection rate estimates can guide policy makers at both state, national or world level to achieve a better management of risk to society. The decisions facing policy makers are very different during early stages of an emerging epidemic where the infection rate is low, middle stages where the rate is rapidly climbing, and later stages where the epidemic curve has flattened to a low and relatively sustainable rate. In this paper we provide relatively efficient pooling methods to both estimate infection rates and identify infected individuals for populations with low infection rates. These estimates may provide significant cost reductions for testing in rural communities, third world countries and other situations where the cost of testing is expensive or testing is not widely available. As we prepare for the second wave of the pandemic this line of work may provide new solutions for both the biomedical community and policy makers at all levels.


title: Graham's Formula for Valuing Growth Stocks

text: Benjamin Graham introduced a very simple formula for valuing a growth stock in 1962. How does it work and why? What is a sensible way to calculate this across many stocks and provide a scoring system to compare stocks amongst each other? We are presenting a methodology here which is put into practice.


title: Climate affects global patterns of COVID-19 early outbreak dynamics

text: Environmental factors, including seasonal climatic variability, can strongly impact on spatio-temporal patterns of infectious disease outbreaks, but relationships between Covid-19 dynamics and climate remain controversial. We assessed the impact of temperature and humidity on the global patterns of Covid-19 early outbreak dynamics during January-March 2020. Here we show that Covid-19 growth rates peaked in temperate regions of the Northern Hemisphere with mean temperature of ~5 C, and specific humidity of 4-6 g/m3 during the outbreak period, while they were lower both in warmer/wetter and colder/dryer regions. Relationships between Covid-19 and climate were robust to the potential confounding effects of air pollution and socio-economic variables, including population size, density and health expenditure. The strong relationship between local climate and Covid-19 growth rates suggests the possibility of seasonal variation in the spatial pattern of outbreaks, with temperate regions of the Southern Hemisphere becoming at particular risk of severe outbreaks during the austral autumn-winter.


title: Optimizing the COVID-19 Intervention Policy in Scotland and the Case for Testing and Tracing

text: Unlike other European countries the UK has abandoned widespread testing and tracing of known SARS-CoV-2 carriers in mid-March. The reason given was that the pandemic was out of control and with wide community based spread it would not be possible to contain it by tracing any longer. Like other countries the UK has since relied on a lockdown as the main measure to contain the virus (or more precisely the reproduction number R at significant economic and social cost. It is clear that this level of lockdown cannot be sustained until a vaccine is available, yet it is not clear what an exit strategy would look like that avoids the danger of a second (or subsequent waves). In this paper we argue that, when used within a portfolio of intervention strategies, widespread testing and tracing leads to significant cost savings compared to using lockdown measures alone. While the effect is most pronounced if a large proportion of the infectious population can be identified and their contacts traced, under reasonable assumptions there are still significant savings even if the fraction of infectious people found by tracing is small. We also present a policy optimization model that finds, for given assumptions on the disease parameters, the best intervention strategy to contain the virus by varying the degree of tracing and lockdown measure (and vaccination once that option is available) over time. We run the model on data fitted to the published COVID-19 outbreak figures for Scotland. The model suggests an intervention strategy that keeps the number of COVID-19 deaths low using a combination of tracing and lockdown. This strategy would only require lockdown measures equivalent to a reduction of R to about 1.8--2.0 if lockdown was used alone, at acceptable economic cost, while the model finds no such strategy without tracing enabled.