title: Two False Negative Test Results in a Symptomatic Patient with a Confirmed Case of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and Suspected Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN)

text: The recent outbreak of COVID-19 has put significant strain on the current health system and has exposed dangers previously overlooked. The pathogen known as severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), is notable for attacking the pulmonary system causing acute respiratory distress, but it can also severely affect other systems in at-risk individuals including cardiovascular compromise, gastrointestinal distress, acute kidney injury, coagulopathies, cutaneous manifestations, and ultimately death from multi-organ failure. Unfortunately, the reliability of negative test results is questionable and the high infectious burden of the virus calls for extended safety precautions, especially in symptomatic patients. We present a confirmed COVID-19 case that was transferred to our burn center for concern of Steven Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) overlap syndrome after having two negative confirmatory COVID-19 tests at an outside hospital. A 58-year-old female with a history of morbid obesity, HTN, gout, CML managed with imatinib, and chronic kidney disease presented as a transfer from a community hospital to our burn center. The patient was admitted to her community hospital with febrile, acute respiratory distress. Imaging and clinical presentation was consistent with COVID-19 and lab tests for the pathogen were ordered. During observation, while waiting for results, she was placed under patient under investigation (PUI) protocol. Once negative results were obtained, the PUI protocol was abandoned despite ongoing symptoms. Subsequently, dermatological symptoms developed and transfer to our burn center was initiated. After a second negative test result, the symptomatic patient was transferred to our burn center for expert wound management. Given the lack of resolve of respiratory symptoms and concern for the burn patient population, the patient was placed in PUI protocol and an internal COVID-19 was ordered. The patient’s initial exam under standard COVID-19 airborne precautions revealed 5% total body surface area of loss of epidermis affecting bilateral thighs, bilateral arms, and face. A dermatopathological biopsy suggested a bullous drug reaction with an erythema multiform-like reaction pattern versus SJS/TEN. Moreover, the internal COVID-19 test returned positive. The delayed positive test results and complicated hospital course with our patient required us to scale back and notify every patient and staff member whom they came in contact with, across multiple institutions. We suggest that whenever a suspected COVID-19 patient is transferred to a specialized center, they should be isolated and re-checked before joining the new patient population for treatment of the unique condition.


title: A Machine Learning Study to Improve Surgical Case Duration Prediction

text: Predictive accuracy of surgical case duration plays a critical role in reducing cost of operation room (OR) utilization. The most common approaches used by hospitals rely on historic averages based on a specific surgeon or a specific procedure type obtained from the electronic medical record (EMR) scheduling systems. However, low predictive accuracy of EMR leads to negative impacts on patients and hospitals, such as rescheduling of surgeries and cancellation. In this study, we aim to improve prediction of operation case duration with advanced machine learning (ML) algorithms. We obtained a large data set containing 170,748 operation cases (from Jan 2017 to Dec 2019) from a hospital. The data covered a broad variety of details on patients, operations, specialties and surgical teams. Meanwhile, a more recent data with 8,672 cases (from Mar to Apr 2020) was also available to be used for external evaluation. We computed historic averages from EMR for surgeon- or procedure-specific and they were used as baseline models for comparison. Subsequently, we developed our models using linear regression, random forest and extreme gradient boosting (XGB) algorithms. All models were evaluated with R-squre (R^2), mean absolute error (MAE), and percentage overage (case duration > prediction + 10 % & 15 mins), underage (case duration < prediction - 10 % & 15 mins) and within (otherwise). The XGB model was superior to the other models by having higher R^2 (85 %) and percentage within (48 %) as well as lower MAE (30.2 mins). The total prediction errors computed for all the models showed that the XGB model had the lowest inaccurate percent (23.7 %). As a whole, this study applied ML techniques in the field of OR scheduling to reduce medical and financial burden for healthcare management. It revealed the importance of operation and surgeon factors in operation case duration prediction. This study also demonstrated the importance of performing an external evaluation to better validate performance of ML models.


title: Potential algorithm of prostate cancer management during the pandemic of coronavirus infection (COVID-19)/ Возможный алгоритм ведения больных раком предстательной железы в условиях пандемии коронавирусной инфекции

text: The World Health Organization has announced the coronavirus infection pandemic (COVID-19), associated with a high risk of severe complications requiring intensive care. The following is a possible algorithm for the choice of treatment tactics for prostate cancer during the COVID-19 pandemic, aimed at achieving 3 main goals: reducing the risk of life-threatening complications of the tumor process, minimizing the risk of “crossing” the profiles of adverse events associated with prostate cancer treatment and viral infection, and diminishing the risk of COVID-19 contamination for prostate cancer patients. The proposed algorithm is a personal view of the authors and is not an official recommendation.


title: Analysis of Covid-19 and non-Covid-19 viruses including influenza viruses to see the influence of intensive preventive measures among Japanese

text: Severe acute respiratory coronavirus 2 (SARS-CoV-2) spread and cause death in worldwide. The preventative measures and infection control are underway throughout the society and there are signs of convergence in some areas. Other viruses as well as SARS-CoV-2 cause cold-like symptoms and spread in winter. However, it is unclear to what extent SARS-CoV-2, influenza virus and other causative viruses have been prevailed since the preventative measures were implemented. In this study, we conducted multiples PCR and quantitative reverse transcription PCR using nasal swabs from 191 patients with cold-like symptoms in Japan to reveal the causative viruses. As a result, at least one virus were detected in 40 out of 191 (21%) patients. Of these, we frequently identified the human rhinovirus / enterovirus (5.8%, n=11), SARS-CoV-2 (4.2%, n=8) and human metapneumovirus (3.7%, n=7). On the other hand, no influenza virus was detected. These results shows the prevalence of causative viruses after the social preventative measures and implies the difference of infectivity between SARS-CoV-2 and influenza virus.


title: Study Data Element Mapping: Feasibility of Defining Common Data Elements Across COVID-19 Studies

text: Background: Numerous clinical studies are now underway investigating aspects of COVID-19. The aim of this study was to identify a selection of national and/or multicentre clinical COVID-19 studies in the United Kingdom to examine the feasibility and outcomes of documenting the most frequent data elements common across studies to rapidly inform future study design and demonstrate proof-of-concept for further subject-specific study data element mapping to improve research data management. Methods: 25 COVID-19 studies were included. For each, information regarding the specific data elements being collected was recorded. Data elements collated were arbitrarily divided into categories for ease of visualisation. Elements which were most frequently and consistently recorded across studies are presented in relation to their relative commonality. Results: Across the 25 studies, 261 data elements were recorded in total. The most frequently recorded 100 data elements were identified across all studies and are presented with relative frequencies. Categories with the largest numbers of common elements included demographics, admission criteria, medical history and investigations. Mortality and need for specific respiratory support were the most common outcome measures, but with specific studies including a range of other outcome measures. Conclusion: The findings of this study have demonstrated that it is feasible to collate specific data elements recorded across a range of studies investigating a specific clinical condition in order to identify those elements which are most common among studies. These data may be of value for those establishing new studies and to allow researchers to rapidly identify studies collecting data of potential use hence minimising duplication and increasing data re-use and interoperability


title: SARS-CoV-2 lethality decreased over time in two Italian Provinces

text: Background Some experts recently reported that SARS-CoV-2 lethality decreased considerably, but no evidence is yet available. This retrospective cohort study aimed to evaluate whether SARS-CoV-2 case-fatality rate decreased with time, adjusting for main potential confounders. Methods and findings We included all SARS-CoV-2 infected subjects diagnosed in Ferrara and Pescara provinces, Italy. Information were collected from local registries, clinical charts, and electronic health records. We compared the case-fatality rate of the subjects diagnosed during April and March, 2020. We used Cox proportional hazards analysis and random-effect logistic regression, adjusting for age, gender, hypertension, type II diabetes, major cardiovascular diseases (CVD), chronic obstructive pulmonary diseases (COPD), cancer and renal disease. The sample included 1946 subjects (mean age 58.8y; 45.7% males). 177 persons deceased, after a mean of 11.7 days of follow-up. From March to April, the case-fatality rate significantly decreased in the total sample (10.8% versus 6.0%; p<0.001), and in any subgroup of patients. Large reductions of the lethality were observed among the elderly (from 30.0% to 13.4%), and subjects with hypertension (23.0% to 12.1%), diabetes (30.3% to 8.4%), CVD (31.5% to 12.1%), COPD (29.7% to 11.4%), and renal disease (32.3% to 11.5%). In April, the adjusted hazard ratio of death was 0.42 (95% Confidence Interval: 0.29-0.60). The mean age of those who died substantially increased from March (77.9y) to April (86.9y). Conclusions In this sample, SARS-CoV-2 case-fatality rate decreased considerably over time, supporting recent claims of a substantial improvement of SARS-CoV-2 clinical management. The findings are inevitably preliminary and require confirmation.


title: Clinical Features of COVID-19 Related Liver Damage

text: BACKGROUND: A recent outbreak of SARS-CoV-2 infection occurs mainly in China, with rapidly increasing the number of cases (namely COVID-19). Abnormal liver functions are frequently present in these patients, here we aimed to clarify the clinical features of COVID-19-related liver damage to provide some references for the clinical treatment. METHODS: In this retrospective, single-center study, we included all confirmed COVID-19 cases in Shanghai Public Health Clinical Center from January 20 to January 31, 2020. The outcomes were followed up until February 19, 2020. A total of 148 cases were analyzed for clinical features, laboratory parameters (including liver function tests), medications and the length of stay. FINDINGS: Of 148 confirmed SARS-CoV-2-infected patients, 49.3% were females and 50.7% were males. The median age was 50.5 years (interquartile range, 36-64). Patients had clinical manifestations of fever (70.1%), cough (45.3%), expectoration (26.7%) at admission. 75 patients (50.7%) showed abnormal liver functions at admission, characterized by an increased of alt, ast, GGT, AKP. Patients (n = 75) who had elevated liver function index were more likely to have a moderate-high degree fever (44% vs 27.4%; p = 0.035) and significantly present in male patients (62.67% vs 38.36%; p = 0.005). The numbers of CD4+ and CD8+ T cells were significantly lower in abnormal liver function group than those in normal liver function group. There was no statistical difference in prehospital medications between normal and abnormal liver function groups, while the utilization rate of lopinavir/ritonavir after admission was significantly higher in patients with emerging liver injury than that in patients with normal liver functions. Importantly, the emerging abnormal liver functions after admission caused a prolonged length of stay. INTERPRETATION: SARS-CoV-2 may cause the liver function damage and the Lopinavir/ritonavir should be applied carefully for the treatment of COVID-19.


title: Quantifying the impacts of human mobility restriction on the spread of COVID-19: an empirical analysis from 344 cities of China

text: Abstract Objective Since the outbreak of novel coronavirus pneumonia (COVID-19), human mobility restriction measures have raised controversies, partly due to inconsistent findings. Empirical study is urgently needed to reliably assess the causal effects of mobility restriction. Methods Our study applied the difference-in-difference (DID) model to assess declines of population mobility at the city level, and used the log-log regression model to examine the effects of population mobility declines on the disease spread measured by cumulative or new cases of COVID-19 over time, after adjusting for confounders. Results The DID model showed that a continual expansion of the relative declines over time in 2020. After four weeks, population mobility declined by 54.81% (interquartile ranges, -65.50% to -43.56%). The accrued population mobility declines were associated with significant reduction of cumulative COVID-19 cases throughout six weeks (i.e., 1% decline of population mobility was associated with 0.72% (95%CI 0.50% to 0.93%) reduce of cumulative cases for one week, 1.42% two weeks, 1.69% three weeks, 1.72% four weeks,1.64% five weeks and 1.52% six weeks). The impact on weekly new cases seemed greater in the first four weeks, but faded thereafter. The effects on cumulative cases differed by cities of different population sizes, with greater effects seen in larger cities. Conclusion Persistent population mobility restrictions are well deserved. However, a change in the degree of mobility restriction may be warranted over time, particularly after several weeks of rigorous mobility restriction. Implementation of mobility restrictions in major cities with large population sizes may be even more important.


title: Microbial natural products as potential inhibitors of SARS-CoV-2 main protease (Mpro)

text: The main protease (Mpro) of the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was subjected to hyphenated pharmacophoric-based and structural-based virtual screenings using a library of microbial natural products (>24,000 compounds). Subsequent filtering of the resulted hits according to the Lipinski’s rules was applied to select only the drug-like molecules. Top-scoring hits were further filtered out depending on their ability to show constant good binding affinities towards the molecular dynamic simulation (MDS)-derived enzyme’s conformers. Final MDS experiments were performed on the ligand–protein complexes (compounds 1–12, Table S1) to verify their binding modes and calculate their binding free energy. Consequently, a final selection of six compounds (1–6) was proposed to possess high potential as anti-SARS-CoV-2 drug candidates. Our study provides insight into the role of the Mprostructural flexibility during interactions with the possible inhibitors and sheds light on the structure-based design of anti-coronavirus disease 2019 (COVID-19) therapeutics targeting SARS-CoV-2.


title: Prevalence of IgG antibodies to SARS-CoV-2 in Wuhan -implications for the ability to produce long-lasting protective antibodies against SARS-CoV-2

text: Background It is to be determined whether people infected with SARS-CoV-2 will develop long-term immunity against SARS-CoV-2 and retain long-lasting protective antibodies after the infection is resolved. This study was to explore to explore the outcomes of IgG antibodies to SARS-CoV-2 in four groups of individuals in Wuhan, China. Methods We included the following four groups of individuals who received both COVID-19 IgM/IgG tests and RT-PCR tests for SARS-CoV-2 from February 29, 2020 to April 29, 2020: 1470 hospitalized patients with COVID-19 from Leishenshan Hospital, Zhongnan Hospital of Wuhan University, and Wuhan No. 7 Hospital, 3832 healthcare providers without COVID-19 diagnosis, 19555 general workers, and 1616 other patients to be admitted to the hospital (N=26473). COVID-19 patients who received IgM/IgG tests <21 days after symptom onset were excluded. Results IgG prevalence was 89.8% (95% CI 88.2-91.3%) in COVID-19 patients, 4.0% (95% CI 3.4-4.7%) in healthcare providers, 4.6 (95% CI 4.3-4.9 %) in general workers, and 1.0% in other patients (p all <0.001 for comparisons with COVID-19 patients). IgG prevalence increased significantly by age among healthcare workers and general workers. Prevalence of IgM antibodies to SARS-CoV-2 was 31.4% in COVID-19 patients, 1.5% in healthcare providers, 1.3% in general workers, and 0.2% in other patients. Conclusions Very few healthcare providers had IgG antibodies to SARS-CoV-2, though a significant proportion of them had been infected with the virus. After SARS-CoV-2 infection, people are unlikely to produce long-lasting protective antibodies against this virus.


title: Exploring alternative medicine options for the prevention or treatment of coronavirus disease 2019 (COVID-19)- A systematic scoping review

text: Background: Coronavirus disease 2019 (COVID-19) is caused by coronavirus 2 (SARS-CoV-2). Symptoms include fever, cough, shortness of breath, muscle pain, pneumonia, and multi-organ failure. The infection spreads from one person to another via respiratory droplets. Alternative medicine (AMs) viz., Ayurveda, Homeopathy, Unani, and Traditional Chinese Medicine (TCM), are being promoted for the prevention of COVID-19. The aim of this systematic scoping review was to identify and summarize the scientific evidences promoting the use of AMs for the prevention of COVID-19. Methods: A comprehensive search of electronic search engines (PubMed and Web of Science) was performed. In addition, freewheeling searches of the government health ministries and government websites was done to retrieve the available information. Records available until 12th March 2020 were considered. Reports proposing the use of AMs for prevention or treatment of COVID-19 across all countries were included. Screening (primary and secondary) of the records and data extraction from the eligible studies were done by a single reviewer followed by a random quality check (10%) by the second reviewer. Results: Overall, 8 records (7 from China and 1 from India) exploring the use of AMs for the prevention or treatment of COVID-19 were identified. Different medicines were explored by different AM systems. Conclusions: Several AMs options are proposed for the prevention or treatment of COVID-19. However, their efficacy and safety still needs scientific validation through rigorous randomized controlled trials. This review may help inform decisions about the importance of research and development of AMs for COVID-19 prevention and treatment.


title: These drugs don’t target the coronavirus—they target us

text: In another example of the blinding speed at which science is moving during the pandemic era, researchers at Aarhus University in Denmark will start a clinical trial of a drug named camostat mesylate tomorrow—barely 1 month after a Cell paper showed the compound can prevent the novel coronavirus, SARS-CoV-2, from entering human cells “If we are to have an impact on the rising epidemic, then we have to act right now,” says Ole Søgaard, the infectious disease physician leading the study


title: Seasonality and uncertainty in COVID-19 growth rates

text: The virus causing COVID-19 has spread rapidly worldwide and threatens millions of lives. It remains unknown if summer weather will reduce its continued spread, thereby alleviating strains on hospitals and providing time for vaccine development. Early insights from laboratory studies of related coronaviruses predicted that COVID-19 would decline at higher temperatures, humidity, and ultraviolet light. Using current, fine-scaled weather data and global reports of infection we developed a model that explained 36% of variation in early growth rates before intervention, with 17% based on weather or demography and 19% based on country-specific effects. We found that ultraviolet light was most strongly associated with lower COVID-19 growth rates. Projections suggest that, in the absence of intervention, COVID-19 will decrease temporarily during summer, rebound by autumn, and peak next winter. However, uncertainty remains high and the probability of a weekly doubling rate remained >20% throughout the summer in the absence of control. Consequently, aggressive policy interventions will likely be needed in spite of seasonal trends.


title: Respiratory infection during lithium and valproate medication: a within-individual prospective study of 50,000 patients with bipolar disorder

text: Objective: In vitro studies have demonstrated that lithium has antiviral properties, but evidence from human studies is scarce. Lithium is used as a mood stabilizer to treat patients with bipolar disorder. Here, the aim was to investigate the association between lithium use and the risk of respiratory infections in patients with bipolar disorder. To rule out the possibility that a potential association could be due to lithium's effect on psychiatric symptoms, we also studied the effect of the most common alternative to lithium to prevent mood episodes in bipolar disorder, valproate. Method: We followed 51,509 individuals diagnosed with bipolar disorder in the Swedish Patient register 2005-2013. We applied a with-individual design using stratified Cox regression to estimate the hazard ratios (HRs) of respiratory infections during treated periods compared with untreated periods. Results: During follow-up, 5,760 respiratory infections were documented in the Swedish Patient Register. The incidence rate was 28% lower during lithium treatment (HR 0.73, 95% CI 0.61-0.86) and 35% higher during valproate treatment (HR 1.35, 95% CI 1.06-1.73) compared with periods off treatment. Conclusions: This study provides real-world evidence that lithium protects against respiratory infections and suggests that the repurposing potential of lithium for antiviral effects is worthy of investigation.


title: Confronting COVID-19: Surging critical care capacity in Italy

text: The current spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Europe threats Italian capacity and that of other national health systems to effectively respond to the needs of patients who require intensive care, mostly due to pneumonia and derived complications from concomitant disease and age. Predicting the surge in capacity has proved difficult due to the requirement of a subtle combination of diverse expertise and difficult choices to be made on selecting robust measures of critical care utilization, and parsimonious epidemic modelling which account for changing government measures. We modelled the required surge capacity of ICU beds in Italy exclusively for COVID-19 patients at epidemic peak. Because new measures were imposed by the Italian government, suspending nearly all non-essential sectors of the economy, we included the potential impacts of these new measures. The modelling considered those hospitalized and home isolated as quarantined, mimicking conditions on the ground. The percentage of patients in intensive care (out of the daily active confirmed cases) required for our calculations were chosen based on clinical relevance and robustness, and this number was consistently on average 9.9% from February 24 to March 6, 2020. Five different scenarios were produced (two positive and three negative). Under most positive scenarios, in which R0 is reduced below 1 (i.e., 0.71), the number of daily active confirmed cases will peak at nearly 89 000 by the early days of April and the total number of intensive care beds exclusively dedicated to COVID-19 patients required in Italy estimated at 8791. Worst scenarios produce unmanageable numbers. Our results suggest that the decisive moment for Italy has come. Jointly reinforcement by the government of the measures approved so far, including home confinement, but even more important the full commitment of the civil society in respecting home confinement, social distancing and hygiene will be key in the next days. Yet, even under the best circumstances, intensive care capacity will need to get closer to 9000 units in the country to avoid preventable mortality. So far, only strong measures were effective in Italy, as shown by our modelling, and this may offer an opportunity to European countries to accelerate their interventions.


title: Large trial yields strongest evidence yet that antiviral drug can help COVID-19 patients

text: A candidate treatment for COVID-19 has shown convincing—albeit modest—benefit for the first time in a large, carefully controlled clinical trial in hospitalized patients The infected people who received remdesivir, an experimental drug made by Gilead Sciences that cripples an enzyme several viruses use to copy their RNA, recovered in an average of 11 days versus 15 in patients who received a placebo “Although a 31% improvement doesn’t seem like a knockout, 100% [success], it is a very important proof of concept,” said Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases (NIAID), during an Oval Office meeting in which President Donald Trump was asked by media about a statement Gilead had released on the results The patients treated with remdesivir also had a lower mortality rate—8% versus 11 6% in the group given the placebo—but this positive trend did not reach statistical significance, Fauci noted (The full results from the trial have not been made public in a preprint or peer-reviewed paper )


title: Development of a Vise with built-in Piezoelectric and Strain Gauge Sensors for Clamping and Cutting Force Measurements

text: Abstract Accurate measurement of static and dynamic forces during machining operations is important in the process monitoring, optimization and prediction of machining quality. Cutting and clamping forces are typically measured separately, for example, through hydraulic clamping force devices and piezoelectric table dynamometers. Since cutting and clamping forces interact throughout machining, both forces need to be measured simultaneously to accurately predict machining quality. This paper proposes a novel force measuring device in the form of a vise with built-in piezoelectric sensors and strain gauges to measure multi-axial clamping and cutting forces simultaneously. A strain concentrating design based on a cross-shaped groove was utilized to attach three strain gauges to measure clamping forces. These locations were chosen for their ability to measure clamping forces in real-time and minimize cross-talks. Piezoelectric sensors were embedded between layers in the vise jaw to measure cutting forces. A prototype of the proposed apparatus was fabricated and used to experimentally investigate sensitivities, bandwidth, clamping forces and cutting forces. The results showed that the proposed device has good performance in measuring clamping and cutting forces in milling operations.


title: Exploration of potential clinical application value and mechanism of Chinese materia medica for tonifying qi and activating blood in COVID-19 with hypoxemia/ 补气活血中药在新型冠状病毒肺炎低氧血症的潜在临床应用价值及其机制浅析

text: For SARS-CoV-2-induced pneumonia, “Diagnosis and Treatment of Novel Coronavirus Pneumonia (trial version 3)” released by the National Health Commission of the People’s Republic of China and the National Administration of Traditional Chinese Medicine on January 22, 2020, first proposed the traditional Chinese medicine (TCM) treatment plan, which was gradually updated to the seventh edition. Patients diagnosed with severe COVID-19 often developed dyspnea and/or hypoxemia one week after onset, requiring respiratory support and circulation support. Through literature research, it was found that Chinese materia medica (CMM) with tonifying qi and activating blood effect could effectively improve hypoxemia of pneumonia-related diseases. This article summarizes the mechanism and clinical application of tonifying qi and activating blood CMM in the treatment of novel coronavirus pneumonia-associated hypoxemia, and provides a reference for clinical treatment of COVID-19.


title: Repurposing Therapeutics for COVID-19: Rapid Prediction of Commercially available drugs through Machine Learning and Docking

text: Background The outbreak of the novel coronavirus disease COVID 19, caused by the SARS-CoV-2 virus has spread rapidly around the globe during the past 3 months. As the virus infected cases and mortality rate of this disease is increasing exponentially, scientists and researchers all over the world are relentlessly working to understand this new virus along with possible treatment regimens by discovering active therapeutic agents and vaccines. So, there is an urgent requirement of new and effective medications that can treat the disease caused by SARS CoV 2. Methods and findings We perform the study of drugs that are already available in the market and being used for other diseases to accelerate clinical recovery, in other words repurposing of existing drugs. The vast complexity in drug design and protocols regarding clinical trials often prohibit developing various new drug combinations for this epidemic disease in a limited time. Recently, remarkable improvements in computational power coupled with advancements in Machine Learning (ML) technology have been utilized to revolutionize the drug development process. Consequently, a detailed study using ML for the repurposing of therapeutic agents is urgently required. Here, we report the ML model based on the Naive Bayes algorithm, which has an accuracy of around 73% to predict the drugs that could be used for the treatment of COVID-19. Our study predicts around ten FDA approved commercial drugs that can be used for repurposing. Among all, we suggest that the antiretroviral drug Atazanavir (DrugBank ID DB01072) would probably be one of the most effective drugs based on the selected criterions. Conclusions Our study can help clinical scientists in being more selective in identifying and testing the therapeutic agents for COVID 19 treatment. The ML based approach for drug discovery as reported here can be a futuristic smart drug designing strategy for community applications.


title: ACE2 fragment as a decoy for novel SARS-Cov-2 virus

text: Novel SARS-Cov-2 enters human cells via interaction between the surface spike (S) glycoprotein and the cellular membrane receptor angiotensin-converting enzyme 2 (ACE2). Using a combination of comparative structural analyses of the binding surface of the S protein to ACE2, docking experiments, and molecular dynamics simulations we computationally identified a minimal, stable fragment of ACE2. This fragment binds to the S protein, is soluble, and appears not to bind to the physiological ligand angiotensinII. These results suggest a possible use of the ACE2 fragment as a decoy that could interfere with viral binding by competition.


title: Dysregulation in mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells

text: How Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infections engage cellular host pathways and innate immunity in infected cells remain largely elusive. We performed an integrative proteo-transcriptomics analysis in SARS-CoV-2 infected HuH7 cells to map the cellular response to the invading virus over time. We identified four pathways, ErbB, HIF-1, mTOR and TNF signaling, among others that were markedly modulated during the course of the SARS-CoV-2 infection in vitro. Western blot validation of the downstream effector molecules of these pathways revealed a significant reduction in activated S6K1 and 4E-BP1 at 72 hours post infection. Unlike other human respiratory viruses, we found a significant inhibition of HIF-1α through the entire time course of the infection, suggesting a crosstalk between the SARS-CoV-2 and the mTOR/HIF-1 signaling. Further investigations are required to better understand the molecular sequelae in order to guide potential therapy in the management of severe COVID-19 patients.


title: Mitigation Policies and Emergency Care Management in Europe's Ground Zero for COVID-19

text: This paper draws from daily death registry data on 4,000 Italian municipalities to investigate two crucial policies that can dramatically affect the toll of COVID-19: the shutdown of non-essential businesses and the management of the emergency care system. Our results, which are robust to controlling for a host of co-factors, offer strong evidence that the closure of service activities is very effective in reducing COVID-19 mortality - this was about 15% lower in municipalities with a 10 percentage points higher employment share in shut down services. Shutting down factories, instead, is much less effective, plausibly because factory workers engage in more limited physical interactions relative to those in the consumer-facing service sector. Concerning the management of the health care system, we find that mortality strongly increases with distance from the intensive care unit (ICU). Municipalities at 10 km from the closest ICU experienced up to 50% higher mortality. This effect - which is largest within the epicenter and in days of abnormally high volumes of calls to the emergency line - underscores the importance of improving pre-hospital emergency services and building ambulance capacity to ensure timely transportation of critical patients to the ICU.


title: The prevalence of common and stress-related mental health disorders in healthcare workers based in pandemic-affected hospitals: a rapid systematic review and meta-analysis

text: Background: Healthcare workers (HCWs) are considered at elevated risk of experiencing mental health disorders in working with patients with COVID-19. Aims: To estimate the prevalence of common mental health disorders in HCWs based in hospitals where pandemic-affected patients were treated. Method: Databases were searched for studies published before 30th March 2020. Quantitative synthesis was used to obtain estimates of the prevalence of mental health disorders in four time windows, determined a priori (the acute phase, i.e. during and up to 1.5 months post-pandemic; 1.5-5.9 months; 6-11.9 months; 12 months and later). Results: Nineteen studies met the review criteria. They predominantly addressed the acute phase of the SARS outbreak in Asia. The most studied outcomes were clinically-significant post-traumatic stress symptoms (PTSS) and general psychiatric caseness. For clinically significant PTSS in the acute phase, the prevalence estimate was 23.4% (95% CI 16.3, 31.2; N=4147; I2=96.2%); in the 12 months plus window, the estimate was 11.9% (8.4, 15.8; N=1136; I2=74.3%). For general psychiatric caseness, prevalence estimates were: acute phase, 34.1% (18.7, 51.4; N=3971; I2=99.1%); 6-12 months, 17.9% (13.1, 23.2; N=223; I2=0.0%); 12 months plus, 29.3% (6.0, 61.0; N=710; I2=97.8%). Conclusions: Mental health disorders are particularly common in HCWs working with pandemic-afflicted patients immediately following a pandemic, but the course of disorders following this period is poorly understood. PTSS remained elevated compared to the general population at 12 months, despite there being some evidence for natural recovery. There was considerable heterogeneity, likely linked to methodological differences. More extended follow up of HCWs is needed.


title: Catalytic cleavage of HEAT and subsequent covalent binding of the tetralone moiety by the SARS-CoV-2 main protease

text: Here we present the crystal structure of SARS-CoV-2 main protease (Mpro) covalently bound to 2-methyl-1-tetralone. This complex was obtained by co-crystallization of Mpro with HEAT (2-(((4-hydroxyphenethyl)amino)methyl)-3,4-dihydronaphthalen-1(2H)-one) in the framework of a large X-ray crystallographic screening project of Mpro against a drug repurposing library, consisting of 5632 approved drugs or compounds in clinical phase trials. Further investigations showed that HEAT is cleaved by Mpro in an E1cB-like reaction mechanism into 2-methylene-1-tetralone and tyramine. The catalytic Cys145 subsequently binds covalently in a Michael addition to the methylene carbon atom of 2-methylene-1-tetralone. According to this postulated model HEAT is acting in a pro-drug-like fashion. It is metabolized by Mpro, followed by covalent binding of one metabolite to the active site. The structure of the covalent adduct elucidated in this study opens up a new path for developing non-peptidic inhibitors.


title: A scenario modeling pipeline for COVID-19 emergency planning

text: Coronavirus disease 2019 (COVID-19) has caused strain on health systems worldwide due to its high mortality rate and the large portion of cases requiring critical care and mechanical ventilation. During these uncertain times, public health decision makers, from city health departments to federal agencies, sought the use of epidemiological models for decision support in allocating resources, developing non-pharmaceutical interventions, and characterizing the dynamics of COVID-19 in their jurisdictions. In response, we developed a flexible scenario modeling pipeline that could quickly tailor models for decision makers seeking to compare projections of epidemic trajectories and healthcare impacts from multiple intervention scenarios in different locations. Here, we present the components and configurable features of the COVID Scenario Pipeline, with a vignette detailing its current use. We also present model limitations and active areas of development to meet ever-changing decision maker needs.


title: The phenotypic changes of Î³Î´ T cells in COVID-19 patients

text: A novel pneumonia-associated respiratory syndrome named coronavirus disease-2019 (COVID-19), which caused by SARS-CoV-2 and broken in Wuhan, China in the end of 2019. Unfortunately, there is no specific antiviral agent or vaccine available to treat SARS-CoV-2 infections. Also, information regarding the immunological characteristics in COVID-19 patients remains limited. Here we collected the blood samples from 18 healthy donors (HD) and 38 COVID-19 patients to analyze changes in {gamma}{delta} T cells. In comparison to HD, the {gamma}{delta} T cells percentage was decreased. {gamma}{delta} T cells are able to immediately respond to SARS-CoV-2 infection and upregulate the activation marker CD25. In addition, the increased expression of CD4 in {gamma}{delta} T cells may serve as a biomarker for the assessment of SARS-CoV-2 infection.


title: Decontamination of filtering facepiece respirators in primary care using medical autoclave

text: Objective: There are widespread shortages of personal protective equipment as a result of the coronavirus disease 2019 (COVID-19) pandemic. Reprocessing filtering facepiece respirators may provide an alternative solution in keeping health care professionals safe. Design: prospective, bench-to-bedside Setting: A primary care-based study using filtering facepiece particles (FFP) type 2 respirators without exhalation valve (3M Aura 1862+, Maco Pharma ZZM002), FFP2 respirators with valve (3M Aura 9322+ and San Huei 2920V), and valved FFP type 3 respirators (Safe Worker 1016). Interventions: All masks were reprocessed using a medical autoclave (34-minute total cycle time of steam sterilization, with 17 minutes at 121 degrees Celsius) and subsequently tested up to 3 times whether these decontaminated respirators retained their integrity (seal check, pressure drop) and ability to filter small particles (0.3-5.0 microns) in the laboratory using a particle penetration test. Results: We tested 32 respirators, and 63 samples for filter capacity. All 27 FFP-2 respirators retained their shape, whereas half of the sterilized FFP-3 respirators (Safe Worker 1116) showed deformities and failed the seal check. The filtering capacity of the 3M Aura 1862 was best retained after 1, 2, and 3 sterilization cycles (0.3 microns: 99.3+/-0.3% (new) versus 97.0+/-1.3, 94.2+/-1.3% or 94.4+/-1.6, p<0.001). Of the other FFP-2 respirators, the San Huei 2920V had 95.5+/-0.7% at baseline versus 92.3+/-1.7% versus 90.0+/-0.7 after one- and two-time sterilization, respectively (p<0.001). The tested FFP-3 respirator (Safe Worker 1016) had a filter capacity of 96.5+/-0.7% at baseline and 60.3+/-5.7% after one-time sterilization (p<0.001). Breathing and pressure resistance tests indicated no relevant pressure changes between respirators that were used once, twice or thrice. Conclusion: This study shows that selected FFP2-type respirators may be reprocessed for use in primary care, as the tested masks retain their shape, ability to retain particles and breathing comfort after decontamination using a medical autoclave.


title: Forecasting the COVID-19 Pandemic with Climate Variables for Top Five Burdening and Three South Asian Countries

text: Background: The novel coronavirus (COVID-19) is now in a horrific situation around the world. Prediction about the number of infected and death cases may help to take immediate action to prevent the epidemic as well as control the situation of a country. The ongoing debate about the climate factors may need more validation with more studies. The climate factors of the top-five affected countries and three south Asian countries have considered in this study to have a real-time forecast and robust validation about the impact of climate variables. Methods: The ARIMA model have included to model the univariate cumulative confirmed and death cases separately. The MLP, ELM and likelihood-based GLM count time series also considered as they consider the external variables as exogenous regressors. As the death count includes zero itself, zero-inflated count time series model has included instead of likelihood-based GLM. The better fitting of the ARIMA model will validate the underwhelm of meteorological factors was the initial hypothesis. The best model has identified through the application and comparison with the real data points. Results: The results depict that there is an influence of meteorological variables like temperature and humidity mostly for all the selected countries cumulative confirm cases excluding Italy and Sri-Lanka. However, the best models for deaths count of each country also identify the impact of meteorological variables for each country. Conclusion: The authors make the sixty days ahead forecast for each country which will be beneficial for the policymakers.


title: CD8+ T cell cross-reactivity against SARS-CoV-2 conferred by other coronavirus strains and influenza virus

text: While individuals infected with coronavirus disease 2019 (COVID-19) manifested a broad range in susceptibility and severity to the disease, the pre-existing immune memory of related pathogens can influence the disease outcome. Here, we investigated the potential extent of T cell cross-reactivity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be conferred by other coronaviruses and influenza virus, and generated a map of public and private predicted CD8+ T cell epitopes between coronaviruses. Moreover, to assess the potential risk of self-reactivity and/or diminished T cell response for peptides identical or highly similar to the host, we identified predicted epitopes with high sequence similarity with human proteome. Lastly, we compared predicted epitopes from coronaviruses with epitopes from influenza virus deposited in IEDB to support vaccine development against different virus strains. We believe the comprehensive in silico profile of private and public predicted epitopes across coronaviruses and influenza viruses will facilitate design of vaccines capable of protecting against various viral infections.


title: Snake deltavirus utilizes envelope proteins of different viruses to generate infectious particles

text: Hepatitis D virus (HDV) is the only known human satellite virus, and it requires hepatitis B virus (HBV) to form infectious particles. Until 2018 HDV was the sole representative of the genus Deltavirus. The subsequent identification of HDV-like agents in non-human hosts indicated a much longer evolutionary history of deltaviruses than previously hypothesized. Interestingly, none of the HDV-like agents were found in co-infection with an HBV-like agent suggesting that these viruses use different helper virus(es). Here we show, using snake deltavirus (SDeV), that HBV represents only a single example of helper viruses for deltaviruses. We cloned the SDeV genome into a mammalian expression plasmid, and by transfection could initiate SDeV replication in cultured snake and mammalian cells. By superinfecting SDeV infected cells with arenaviruses, or by transfecting different viral surface proteins, we could induce infectious SDeV particle production. Our findings indicate that deltaviruses can likely use a multitude of helper viruses or even viral glycoproteins to form infectious particles. Persistent and recurrent infections would be beneficial for the spread of deltaviruses. It seems plausible that new human and veterinary disease associations with deltavirus infections will be identified in the future.


title: Mass casualty event scenarios and political shifts: 2020 election outcomes and the U.S. COVID-19 pandemic

text: COVID-19 models indicate a mass casualty event may potentially occur in the United States. Among numerous social and economic changes, the potential to reshape the political landscape exists. The theoretical perspective of politics-administration dichotomy is used to examine the rhetoric, power, and authority of public health messages during the pandemic. This study considers political shifts using state-level data on population, historical voter turnout, and projected COVID-19 cases number coupled with national-level data on voter participation by age group and COVID-19 fatality rates. Developing a formula to calculate these data, we project the extent to which the number of voters from each party could diminish. The analysis shows the potential for significant political changes due to the disproportionate loss of older voters in key swing states in the months leading to the 2020 presidential election.


title: The global viralization of policies to contain the spreading of the COVID-19 pandemic: analyses of school closures and first reported cases.

text: Background With the exposure to the COVID-19 pandemic, countries swiftly implemented a variety of health policies. In this work we examine how rapid countries responded to this pandemic using two events: the day in which the first case of COVID-19 was reported, and first day in which countries used school closure as one of the measures to avoid outbreaks. Methods We compiled information from multiple sources, from December 31st 2019 to June 1st 2020, to trace when 172 countries reported their first COVID-19 case and implemented school closure to contain outbreaks. We applied cross-national Weibull survival analysis to evaluate the global speed of detection of first COVID-19 reported cases and school closure. We also assessed how health systems, globalization, economic development, political systems, and economic integration to China, Republic of Korea and Italy increased the speed of adoption. Results Ten days after the World Health Organization (WHO) declared COVID-19 to be an international emergency, countries were 28 (95% CI: 12,77) times more likely to report first COVID-19 cases and 42 (95% CI: 22,90) times more likely to close schools. One standard deviation increase in the epidemic security index rises the rate of report first cases by 37% (Hazard Ratio (HR) 1.37 (95% CI: 1.09,1.72) and delays the adoption for school closures by 36% (HR 0.64 (95% CI:0.50,0.82). One standard deviation increase in the globalization index augments the adoption for school closures by 74% (HR 1.74 (95% CI:1.34,2.24). Conclusion. After the WHO declared a global emergency, countries were unprecedently acting very rapidly. While countries more globally integrated were swifter in closing schools, countries with better designed health systems to tackle epidemics were slower in adopting it. More studies are needed to assess how the speed of school closures and other policies will affect the development of the pandemic.


The position statement of the Polish Society of Gastroenterology and the Polish National Consultant in Gastroenterology regarding the management of patients with inflammatory bowel disease during the COVID-19 pandemic


title: Ease COVID-19 border controls, say EU CEOs

text: Twenty-three European CEOs, including several from the chemical industry, have signed a statement calling on European politicians to ease border restrictions designed to control COVID-19 so that the transportation of essential goods and services across the region can flow freely Extra border checks and restrictions are slowing deliveries across Europe, and a coordinated approach to speed the transportation of essential goods is required, the CEOs write They are urging the European Commission (EC) to move quickly to implement its recently announced Green Lane initiative, which gives trucks carrying essential goods priority at borders BASF CEO Martin Brudermüller and Solvay CEO Ilham Kadri are among the signatories, along with distribution company leaders and CEOs of chemical industry customers The statement voices industry’s frustration with EU politicians and follows an open letter sent to EC president Ursula von der Leyen on April 10 by Marco Mensink, director of the chemical trade association View: PDF ;Full Text HTML


title: Analysis of Genetic Host Response Risk Factors in Severe COVID-19 Patients

text: BACKGROUND Epidemiological studies indicate that as many as 20% of individuals who test positive for COVID-19 develop severe symptoms that can require hospitalization. These symptoms include low platelet count, severe hypoxia, increased inflammatory cytokines and reduced glomerular filtration rate. Additionally, severe COVID-19 is associated with several chronic co-morbidities, including cardiovascular disease, hypertension and type 2 diabetes mellitus. The identification of genetic risk factors that impact differential host responses to SARS-CoV-2, resulting in the development of severe COVID-19, is important in gaining greater understanding into the biological mechanisms underpinning life-threatening responses to the virus. These insights could be used in the identification of high-risk individuals and for the development of treatment strategies for these patients. METHODS As of June 6, 2020, there were 976 patients who tested positive for COVID-19 and were hospitalized, indicating they had a severe response to SARS-CoV-2. There were however too few patients with a mild form of COVID-19 to use this cohort as our control population. Instead we used similar control criteria to our previous study looking at shared genetic risk factors between severe COVID-19 and sepsis, selecting controls who had not developed sepsis despite having maximum co-morbidity risk and exposure to sepsis-causing pathogens. RESULTS Using a combinatorial (high-order epistasis) analysis approach, we identified 68 protein-coding genes that were highly associated with severe COVID-19. At the time of analysis, nine of these genes have been linked to differential response to SARS-CoV-2. We also found many novel targets that are involved in key biological pathways associated with the development of severe COVID-19, including production of pro-inflammatory cytokines, endothelial cell dysfunction, lipid droplets, neurodegeneration and viral susceptibility factors. CONCLUSION The variants we found in genes relating to immune response pathways and cytokine production cascades, were in equal proportions across all severe COVID-19 patients, regardless of their co-morbidities. This suggests that such variants are not associated with any specific co-morbidity, but are common amongst patients who develop severe COVID-19. Among the 68 severe COVID-19 risk-associated genes, we found several druggable protein targets and pathways. Nine are targeted by drugs that have reached at least Phase I clinical trials, and a further eight have active chemical starting points for novel drug development. Several of these targets were particularly enriched in specific co-morbidities, providing insights into shared pathological mechanisms underlying both the development of severe COVID-19, ARDS and these predisposing co-morbidities. We can use these insights to identify patients who are at greatest risk of contracting severe COVID-19 and develop targeted therapeutic strategies for them, with the aim of improving disease burden and survival rates.


title: Tough times and Miles to go before we sleep- Corona warriors

text: The world has changed due to COVID-19 pandemic. Global spread of COVID-19 has overwhelmed all health systems and has incurred widespread social and economic disruption. The authorities are struggling to ramp up the healthcare systems to overcome it. Anaesthesiologists are facing long duty hours, have fear of bringing disease home to their families, being companion to critically ill patients on long term life support, being on front line of this pandemic crisis, may take toll on all aspects of health of corona warriors- physical, mental, social as well as the emotional.At this juncture, we must pause and ask this question to ourselves, 'Buried under stress, are we okay?'.


title: Is tracking and modeling Covid-19 infection dynamics for Bangladesh using daily data feasible?

text: Given the low Covid-19 testing coverage in the country, this study tested whether the daily change in the number of new Covid-19 cases is due to increase (or decrease) in the number of tests done daily. We performed Granger causality test based on vector autoregressive models on Bangladesh case and test numbers between 8 March and 5 June 2020, using publicly available data. The test results show that the daily number of tests Granger-cause the number of new cases (p <0.001), meaning the daily number of new cases is perhaps due to an increase in test capacity rather than a change in the infection rates. From the results of this test we can infer that if the number of daily tests does not increase substantially, data on new infections will not give much information for understanding covid-19 infection dynamics in Bangladesh.


title: Sex-specific differences in COVID-19 testing, cases and outcomes: a population-wide study in Ontario, Canada

text: In this population-wide study in Ontario, Canada we report on all 194,372 unique residents who received testing for SARS-CoV-2 between January 23, 2020 and April 28, 2020. We found that while more women than men were tested for SARS-CoV-2, men had a higher rate of laboratory-confirmed COVID-19 infection, hospitalization, ICU admission and death. These findings were consistent even with age adjustment, suggesting that the observed differences in outcomes between women and men were not explained by age or systematic differences in testing by sex. Instead, they may be due to sex-based immunological or other gendered differences, such as higher rates of smoking leading to cardiovascular disease.


title: High frequency of SARS-CoV-2 RNAemia and association with severe disease

text: Background: Detection of SARS-CoV-2 RNA in the blood, also known as RNAemia, has been reported, but its prognostic implications are not well understood. This study aimed to determine the frequency of SARS-CoV-2 RNA in plasma and its association with the clinical severity of COVID-19. Methods: An analytical cross-sectional study was performed in a single-center tertiary care institution in northern California and included consecutive inpatients and outpatients with COVID-19 confirmed by detection of SARS-CoV-2 RNA in nasopharyngeal swab specimens. The prevalence of SARS CoV-2 RNAemia and the strength of its association with clinical severity variables were examined and included the need for transfer to an intensive care unit (ICU), mechanical ventilation and 30-day all-cause mortality. Results: Paired nasopharyngeal and plasma samples were included from 85 patients. The overall median age was 55 years, and individuals with RNAemia were older than those with undetectable SARS-CoV-2 RNA in plasma (63 vs 50 years; p=0.001). Comorbidities were frequent including obesity (37.7%), hypertension (30.6%) and diabetes mellitus (22.4%). RNAemia was detected in a total of 28/85 (32.9%) individual patients, including 22/28 (78.6%) who required hospital admission. RNAemia was detected more frequently in individuals who developed severe disease including the need for ICU transfer (32.1% vs 14.0%; p=0.05), mechanical ventilation (21.4% vs 3.5%; p=0.01) and 30-day all-cause mortality (14.3% vs 0%; p=0.01). No association was detected between RNAemia and estimated levels of viral RNA in the nasopharynx. An additional 121 plasma samples from 28 individuals with RNAemia were assessed longitudinally, and RNA was detected for a maximum duration of 10 days. Conclusion: This study demonstrated a high proportion of SARS-CoV-2 RNAemia, and an association between RNAemia and clinical severity suggesting the potential utility of plasma viral testing as a prognostic indicator for COVID-19.


title: A content analysis of Chinese news coverage on COVID-19 and tourism

text: News coverage plays a significant role in the tourism industry. 2019 Coronavirus Disease (COVID-19) has severely affected the tourism-related businesses and has been featured in Chinese news coverage. This research studied 499 newspaper articles through automated content analysis. Nine key themes were identified, including COVID-19's impact on tourism, people's sentiment, control of tourism activities and cultural venues, the role of the hospitality industry, national command and local response, tourism disputes and solutions, corporate self-improvement strategies, government assistance, and post-crisis tourism product. This research provides insights into future investigations of the tourism crisis related to an epidemic.


Ethical and responsible tourism: managing sustainability in local tourism destinations


title: A Decision Analytic Approach for Social Distancing Policies During the COVID-19 Pandemic

text: The COVID-19 pandemic has become a crucial public health issue in many countries including the United States. In the absence of the right vaccine strain and sufficient antiviral stockpiles on hand, nonpharmaceutical interventions have become valuable public health tools at the early stages of the pandemic and they are employed by many countries across the globe. These interventions are designed to increase social distancing between individuals to reduce the transmission of the virus and eventually dampen the burden on the healthcare system. The virus transmissibility is a function of the average number of contacts individuals have in their communities and it is highly dependent on population density and daily mobility patterns, along with other social factors. These show significant variation across the United States. In this article, we study the effectiveness of social distancing measures in communities with different population density. Specifically, first we show how the empirical estimation of reproduction number differs for two completely different states, thus the experience of the COVID-19 outbreak is drastically different, suggesting different outbreak growth rates in practice. Second, we develop an age-structured compartmental model for simulating the disease spread to demonstrate the variation in the observed outbreak characteristics. We find that early trigger and late trigger options present a trade-off between the peak magnitude and the overall death toll of the outbreak which may also vary across different populations.


title: Identifying Explosive Cases with Unsupervised Machine Learning

text: An analysis of a combined dataset of Wave 1 and 2 cases, aligned at approximately Local Time Zero + 2 months with unsupervised machine learning methods such as PCA and deep autoencoder dimensionality reduction allows to clearly separate milder background cases from those with more rapid and aggressive onset of the epidemics. The analysis and findings of the study can be used in evaluation of possible epidemiological scenarios and as an effective modeling tool to design corrective and preventative measures to avoid developments with potentially heavy impact.


title: Forecasting undetected COVID-19 cases in Small Island Developing States using Bayesian approach

text: In dealing with the COVID-19, the fundamental question is how many actually undetected cases are going around regarding the capabilities of current health systems to contain the virus?. Due to a large number of asymptomatic cases, most COVID-19 cases are possibly undetected. For that reason, this study aims to provide an e[ff]icient, versatile, easy to compute, and robust estimator for the number of undetected cases using Bayes theorem based on the actual COVID-19 cases. This theorem is applied to 25 Small Island Developing States (SIDS) due to SIDS vulnerability. The results in this study forecast that possibly undetected COVID-19 cases are approximately 4 times larger than the numbers of actual COVID-19 cases as observed. This finding highlights the importance of using modeling tool to get the better and comprehensive of current COVID-19 cases and to take immediately precaution approaches to mitigate the growing numbers of COVID-19 cases as well.


title: Novel NGS Pipeline for Virus Discovery from a Wide Spectrum of Hosts and Sample Types

text: The study of the microbiome data holds great potential for elucidating the biological and metabolic functioning of living organisms and their role in the environment. Metagenomic analyses have shown that humans, along with e.g. domestic animals, wildlife and arthropods, are colonized by an immense community of viruses. The current Coronavirus pandemic (COVID-19) heightens the need to rapidly detect previously unknown viruses in an unbiased way. The increasing availability of metagenomic data in this era of next-generation sequencing (NGS), along with increasingly affordable sequencing technologies, highlight the need for reliable and comprehensive methods to manage such data. In this article, we present a novel stand-alone pipeline called LAZYPIPE for identifying both previously known and novel viruses in host-associated or environmental samples and give examples of virus discovery based on it. LAZYPIPE is a Unix-based pipeline for automated assembling and taxonomic profiling of NGS libraries implemented as a collection of C++, Perl, and R scripts.


title: Generation of antibodies against COVID-19 virus for development of diagnostic tools

text: The COVID-19 China coronavirus started in Dec 2019 was challenged by the lack of accurate serological diagnostic tool for this deadly disease to quickly identify and isolate the infected patients. The generation of COVID-19-specific antibodies is essential for such tasks. Here we report that polyclonal and monoclonal antibodies were generated by immunizing animals with synthetic peptides corresponding to different areas of Nucleoprotein (N) of COVID-19. The specificities of the COVID-19 antibodies were assessed by Western Blot analysis against NPs from COVID-19, MERS and SARS. Antibodies were used for immunohistochemistry staining of the tissue sections from COVID-19 infected patient, as a potential diagnostic tool. A Sandwich ELISA kit was quickly assembled for quantitation of the virus/NP of COVID-19 concentrations in the vaccine preparations. Development of POCT is also aggressively undergoing.


Will COVID-19 Mark the End of an Egalitarian National Health Service?


title: Severe Acute Respiratory Syndrome Coronavirus 2: Genomic Observations and Emerging Therapies

text: Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of the disease COVID-19, first emerged in late December 2019 in China, and has subsequently become a pandemic with unprecedented clinical impact The virus appears to more severely affect older individuals and those with co-morbid medical conditions, specifically those with chronic lung disease, obesity, heart failure and diabetes Fortunately, children appear to be less severely affected, though mortality and severe disease have been reported In addition, children's role in spreading the disease (potentially through asymptomatic shedding of the virus) remains an important area requiring further investigation The emergence of SARS-CoV-2 has highlighted the importance of metagenomic next generation sequencing as a tool for pandemic investigation Though no proven therapeutic options currently exist, ongoing genomic and clinical trial data may help inform the identification and development of both repurposed and novel therapeutic agents for use in this disease


title: Associations of ambient air pollutants and meteorological factors with COVID-19 transmission in 31 Chinese provinces: A time-series study

text: Background: Evidence regarding the effects of ambient air pollutants and meteorological factors on COVID-19 transmission is limited. Objectives: To explore the associations of air pollutants and meteorological factors with COVID-19 confirmed cases across 31 Chinese provinces during the outbreak period. Methods: The number of COVID-19 confirmed cases, air pollutant concentrations and meteorological factors in 31 Chinese provinces from January 25 to February 29, 2020 were extracted from authoritative electronic databases. The associations were estimated for a single-day lag (lag0-lag6) as well as moving averages lag (lag01-lag05) using generalized additive mixed models (GAMMs), adjusted for time trends, day of the week, holidays and meteorological variables. Region-specific analyses and meta-analysis were conducted in five selected regions with diverse air pollution levels and weather conditions. Nonlinear exposure-response analyses were performed. Results: We examined 77,578 COVID-19 confirmed cases across 31 Chinese provinces during the study period. An increase of each interquartile range in PM2.5, PM10, SO2, NO2, O3 and CO at lag4 corresponded to 1.40 (1.37-1.43), 1.35 (1.32-1.37), 1.01 (1.00-1.02), 1.08 (1.07-1.10), 1.28 (1.27-1.29) and 1.26 (1.24-1.28) odds ratios (ORs) of daily COVID-19 confirmed new cases, respectively. For 1 oc, 1% and 1 m/s increase in temperature, relative humidity and wind velocity, the ORs were 0.97 (0.97-0.98), 0.96 (0.96-0.97), and 0.94 (0.92-0.95), respectively. The estimates of PM2.5, PM10, NO2 and all meteorological factors remained statistically significant after meta-analysis for the five selected regions. The exposure-response relationships showed that higher concentrations of air pollutants and lower meteorological factors were associated with daily COVID-19 confirmed new cases increasing. Conclusions: Higher air pollutant concentrations and lower temperature, relative humidity and wind velocity may favor COVID-19 transmission. As summer months are arriving in the Northern Hemisphere, the environmental factors and implementation of public health control measures may play an optimistic role in controlling COVID-19 epidemic.


title: Toward sustainable learning during school suspension: Socioeconomic, occupational aspirations, and learning behavior of vietnamese students during COVID-19

text: The overspread of the novel coronavirus-SARS-CoV-2-over the globe has caused significant damage to manufacturing and service businesses, regardless of whether they are commercial, public, or not-for-profit sectors. While both the short-term and long-term impacts of most companies can be approximately measured or estimated, it is challenging to address the enduring effects of COVID-19 on teaching and learning activities. The target of this research is to investigate students' manners of studying at home during the school suspension time as a result of COVID-19. Through analyzing original survey data from 420 K6-12 students in Hanoi, Vietnam, this work demonstrates the different learning habits of students with different socioeconomic statuses and occupational aspirations during the disease's outbreak. In particular, we featured the differences in students' learning behaviors between private schools and public schools, as well as between students who plan to follow STEM-related careers and those who intend to engage in social science-related careers. The empirical evidence of this study can be used for the consideration of the local government to increase the sustainability of coming policies and regulations to boost students' self-efficacy, as it will affect 1.4 million students in Hanoi, as well as the larger population of nearly 10 million Vietnamese students. These results can also be the foundation for future investigations on how to elevate students' learning habits toward Sustainable Development Goal 4 (SDG4)-Quality Education-especially in fanciful situations in which the regular school operation has been disrupted, counting with limited observation and support from teachers and parents.


title: Long time frames to detect the impact of changing COVID-19 control measures

text: Background: Many countries have implemented population-wide interventions such as physical distancing measures, in efforts to control COVID-19. The extent and success of such measures has varied. Many jurisdictions with declines in reported COVID-19 cases are moving to relax measures, while others are continuing to intensify efforts to reduce transmission. Aim: We aim to determine the time frame between a change in COVID-19 measures at the population level and the observable impact of such a change on cases. Methods: We examine how long it takes for there to be a substantial difference between the cases that occur following a change in control measures and those that would have occurred at baseline. We then examine how long it takes to detect a difference, given delays and noise in reported cases. We use changes in population-level (e.g., distancing) control measures informed by data and estimates from British Columbia, Canada. Results: We find that the time frames are long: it takes three weeks or more before we might expect a substantial difference in cases given a change in population-level COVID-19 control, and it takes slightly longer to detect the impacts of the change. The time frames are shorter (11-15 days) for dramatic changes in control, and they are impacted by noise and delays in the testing and reporting process, with delays reaching up to 25-40 days. Conclusion: The time until a change in broad control measures has an observed impact is longer than is typically understood, and is longer than the mean incubation period (time between exposure than onset) and the often used 14 day time period. Policy makers and public health planners should consider this when assessing the impact of policy change, and efforts should be made to develop rapid, consistent real-time COVID-19 surveillance.


title: Chest high resolution CT manifestations of early stage corona virus disease 2019/ 新型冠状病毒肺炎早期胸部高分辨率CT表现

text: Objective: To explore high chest resolution CT (HRCT) manifestations of early stage corona virus disease 2019 (COVID-2019). Methods: Chest HRCT findings of 31 COVID-2019 patients were retrospectively analyzed. Results: Chest HRCT showed vary degrees changes of pneumonia within 1 week of onset. Multiple lesions (3 or more lesions) were found in 23 cases. Lesions affected 2 and more pulmonary lobes were observed in 24 cases, while single pulmonary lobe involvement was observed in 7 cases. Multiple ground-glass opacity (GGO) was noticed in 22 patients, while in other 9 cases multiple GGO mixed consolidation were found, all had fuzzy boundaries. The lesions presented at peripheral lungs in 25 cases, while in 6 cases presented at peripheral combined and central lungs. Lesions of irregular morphology were observed in 26 cases, while rounded morphology and sphericity were observed in the other 5 cases. Air bronchogram was noticed in 26 cases, thickening vascular in the lesions were found in 29 case, thickened intralobular interstitium in 24 cases, thickened interlobular interstitium in 6 cases, centrilobular nodules in 2 cases and a small amount of pleural effusion in 1 case. Conclusion: The early chest HRCT manifestations of COVID-2019 have certain characteristics. Combination of clinical history and chest HRCT manifestations is conducive to early diagnosis COVID-2019.


title: Effect of Dexamethasone in Hospitalized Patients with COVID-19: Preliminary Report

text: Background: Coronavirus disease 2019 (COVID-19) is associated with diffuse lung damage. Corticosteroids may modulate immune-mediated lung injury and reducing progression to respiratory failure and death. Methods: The Randomised Evaluation of COVID-19 therapy (RECOVERY) trial is a randomized, controlled, open-label, adaptive, platform trial comparing a range of possible treatments with usual care in patients hospitalized with COVID-19. We report the preliminary results for the comparison of dexamethasone 6 mg given once daily for up to ten days vs. usual care alone. The primary outcome was 28-day mortality. Results: 2104 patients randomly allocated to receive dexamethasone were compared with 4321 patients concurrently allocated to usual care. Overall, 454 (21.6%) patients allocated dexamethasone and 1065 (24.6%) patients allocated usual care died within 28 days (age-adjusted rate ratio [RR] 0.83; 95% confidence interval [CI] 0.74 to 0.92; P<0.001). The proportional and absolute mortality rate reductions varied significantly depending on level of respiratory support at randomization (test for trend p<0.001): Dexamethasone reduced deaths by one-third in patients receiving invasive mechanical ventilation (29.0% vs. 40.7%, RR 0.65 [95% CI 0.51 to 0.82]; p<0.001), by one-fifth in patients receiving oxygen without invasive mechanical ventilation (21.5% vs. 25.0%, RR 0.80 [95% CI 0.70 to 0.92]; p=0.002), but did not reduce mortality in patients not receiving respiratory support at randomization (17.0% vs. 13.2%, RR 1.22 [95% CI 0.93 to 1.61]; p=0.14). Conclusions: In patients hospitalized with COVID-19, dexamethasone reduced 28-day mortality among those receiving invasive mechanical ventilation or oxygen at randomization, but not among patients not receiving respiratory support.


title: Analysis of COVID-19 cases and associated ventilator requirement in Indian States

text: Analysis of COVID-19 cases and prediction of quantity of associated ventilator requirement is very relevant during this pandemic. This paper presents a method for predictive estimation of ventilator requirement for COVID-19 patients in Indian states. It uses ARIMA (Autoregressive Integrated Moving Average) model for predicting the future cumulative cases and daily fatality. Taking cue from this, ventilator requirement is estimated for each state. State wise estimation of ventilator is important because public healthcare system in India is managed at state level. Dataset on Novel Corona Disease 2019 in India from Kaggle website is used in this work.


title: Detection of spreader nodes and ranking of interacting edges in Human-SARS-CoV protein interaction network

text: The entire world has recently witnessed the commencement of coronavirus disease 19 (COVID-19) pandemic. It is caused by a novel coronavirus (n-CoV) generally distinguished as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). It has exploited human vulnerabilities to coronavirus outbreak. SARS-CoV-2 promotes fatal chronic respiratory disease followed by multiple organ failure which ultimately puts an end to human life. No proven vaccine for n-CoV is available till date in spite of significant research efforts worldwide. International Committee on Taxonomy of Viruses (ICTV) has reached to a consensus that the virus SARS-CoV-2 is highly genetically similar to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) outbreak of 2003. It has been reported that SARS-CoV has ∼89% genetic similarities with n-CoV. With this hypothesis, the current work focuses on the identification of spreader nodes in SARS-CoV protein interaction network. Various network characteristics like edge ratio, neighborhood density and node weight have been explored for defining a new feature spreadability index by virtue of which spreader nodes and edges are identified. The selected top spreader nodes having high spreadability index have been also validated by Susceptible-Infected-Susceptible (SIS) disease model. Initially, the proposed method is applied on a synthetic protein interaction network followed by SARS-CoV-human protein interaction network. Hence, key spreader nodes and edges (ranked edges) are unmasked in SARS-CoV proteins and its connected level 1 and level 2 human proteins. The new network attribute spreadability index along with generated SIS values of selected top spreader nodes when compared with the other network centrality based methodologies like Degree centrality (DC), Closeness centrality (CC), Local average centrality (LAC) and Betweeness centrality (BC) is found to perform relatively better than the existing-state-of-art.


title: The hypothalamus as a hub for SARS-CoV-2 brain infection and pathogenesis

text: Most patients with COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), display neurological symptoms, and respiratory failure in certain cases could be of extra-pulmonary origin. Hypothalamic neural circuits play key roles in sex differences, diabetes, hypertension, obesity and aging, all risk factors for severe COVID-19, besides being connected to olfactory/gustative and brainstem cardiorespiratory centers. Here, human brain gene-expression analyses and immunohistochemistry reveal that the hypothalamus and associated regions express angiotensin-converting enzyme 2 and transmembrane proteinase, serine 2, which mediate SARS-CoV-2 cellular entry, in correlation with genes or pathways involved in physiological functions or viral pathogenesis. A post-mortem patient brain shows viral invasion and replication in both the olfactory bulb and the hypothalamus, while animal studies indicate that sex hormones and metabolic diseases influence this susceptibility.


title: The effects of misleading media reports about COVID-19 on Chinese tourists’ mental health: a perspective article

text: The novel coronavirus (COVID-19) has been declared apublic health emergency of international concern by the World Health Organization. This pandemic has since saturated the headlines of major international media channels that disseminate information to global citizens. However, some media coverage of COVID-19 has negatively influenced Chinese travellers’ mental health due to the outbreak having been labelled “Chinese virus pandemonium.” Key world leaders have also parroted such sensationalism; for example, President Donald Trump called COVID-19 the “Chinese virus”. This discriminatory labelling has resulted in violent attacks on Chinese international travellers and students. This perspective article explores how misleading and discriminatory media reports may affect the mental well-being of ethnically Chinese travellers during the global COVID-19 pandemic.


title: Characterisation of the bovine enteric calici-like virus, Newbury agent 1

text: Abstract The bovine enteric calici-like virus, Newbury agent 1 (NA1) was characterised to determine if it is a member of the Caliciviridae and to establish its antigenic relationship to the established bovine enteric calicivirus Newbury agent 2 (NA2). Solid phase immune electron microscopy (SPIEM) allowed quantification of NA1 virions and identification of faecal samples with optimal virus levels. NA1 particles were 36.6 nm in diameter, had an indefinite surface structure resembling that of human small round structured viruses (SRSVs), and a buoyant density of 1.34 g ml−1. A single capsid protein of 49.4 kDa was detected by Western blotting in purified NA1 preparations prepared from post-infection but not pre-infection faecal samples and with post- but not pre-infection sera. NA1 was antigenically unrelated to the bovine enteric calicivirus NA2 by SPIEM. These properties were consistent with classification of NA1 within the Caliciviridae but demonstrated heterogeneity in the capsid composition of bovine enteric caliciviruses.


title: Collateral damage: the impact on cancer outcomes of the COVID-19pandemic

text: Background: Cancer diagnostics and surgery have been disrupted by the response of healthcare services to the COVID-19 pandemic. Progression of cancers during delay will impact on patient long-term survival. Methods: We generated per-day hazard ratios of cancer progression from observational studies and applied these to age-specific, stage-specific cancer survival for England 2013-2017. We modelled per-patient delay of three months and six months and periods of disruption of one year and two years. Using healthcare resource costing, we contextualise attributable lives saved and life years gained from cancer surgery to equivalent volumes of COVID-19 hospitalisations. Findings: Per year, 94,912 resections for major cancers result in 80,406 long-term survivors and 1,717,051 life years gained. Per-patient delay of six months would cause attributable death of 10,555 of these individuals with loss of 205,024 life years. For cancer surgery, average life years gained (LYGs) per patient are 18.1 under standard conditions and 15.9 with a delay of six months (a loss of 2.3 LYG per patient). Taking into account units of healthcare resource (HCRU), surgery results on average per patient in 2.25 resource-adjusted life years gained (RALYGs) under standard conditions and 1.98 RALYGs following delay of six months. For 94,912 hospital COVID-19 admissions, there are 474,505 LYGs requiring of 1,097,937 HCRUs. Hospitalisation of community-acquired COVID-19 patients yields on average per patient 5.0 LYG and 0.43 RALYGs. Interpretation: Delay of six months in surgery for incident cancers would mitigate 43% of life years gained by hospitalisation of an equivalent volume of admissions for community acquired COVID-19. This rises to 62% when considering resource-adjusted life-years gained. To avoid a downstream public health crisis of avoidable cancer deaths, cancer diagnostic and surgical pathways must be maintained at normal throughput, with rapid attention to any backlog already accrued. Funding: Breast Cancer Now, Cancer Research UK, Bobby Moore Fund for Cancer Research, National Institute for Health Research (NIHR)


title: COVID 19 Pandemic: A Real-time Forecasts & Prediction of Confirmed Cases, Active Cases using the ARIMA model &Public Health in West Bengal, India.

text: Abstract Background: COVID-19 is an emerging infectious disease which has been declared a Pandemic by the World Health Organization (WHO) on March 11 2020. This pandemic has spread over the world in more than 200 countries. India is also adversely affected by this pandemic, and there are no signs of slowing down of the virus in coming time. The absence of a vaccine for COVID-19 is making the situation worse for the already overstretched Indian public health care system. As economic burden makes it increasingly difficult for our country to continue imposing control measures, it is vital for states like West Bengal to make predictions using time series forecasting for the upcoming cases , test kits , health care and estimated the requirement of Quarantine centers, isolation beds, ICU beds and ventilators for COVID-19 patients . Objective: This study is forecasting the confirmed and active cases for COVID-19 until August, using time series ARIMA model & Public Health in West Bengal, India. Methods: We used ARIMA model, and Auto ARIMA model for forecasting confirmed and active cases till the end of August month using time series data of COVID-19 cases in West Bengal, India from March 1, 2020, to June 4, 2020. Discussion and Conclusion: This forecasts show a very crucial situation for West Bengal in coming days and, the actual numbers can go higher than our estimates of confirmed case as Lockdown 5.0 & Unlock 1.0 will be implemented from 1st June 2020 in India, West Bengal will be observing a partial lift of the lockdown and in that case, there will be a surge in the number of daily confirmed and active cases. The requirement of Health care sector needs to be further improved isolation beds, ICUs and ventilators will also be needed to increase in that scenario. Inter State & Intra State Movement restrictions are lifted. Hence, Migrants returning to their homes due to loss of livelihood and income in the lockdown period may lead to a rise in the number of cases, which could not be accounted for in our projections. We suggest more of Public-Private Partnership (PPP) model in the health sector to accommodate COVID-19 patients adequately and reduce the burden of the already overstretched Indian public health care system, which will directly or indirectly affect the States in the time of crisis. Keywords: COVID 19, India,West Bengal, Forecast, ARIMA, Public Health, State-level analysis.


title: Tracheostomy Considerations during the COVID-19 Pandemic

text: OBJECTIVE: To compile current best practices regarding tracheostomy decision making, care, and technical performance during the global COVID-19 pandemic. DATA SOURCES: Articles listed in PubMed and Google sources for up-to-date information. REVIEW METHODS: All sources presenting objective evidence related to the topic were reviewed and distilled. CONCLUSIONS: Tracheostomy in patients with coronavirus disease should be a rare event yet one that requires significant decision making and procedural deliberation. Indications for surgery must be balanced by risk of disease transmission to health care workers. Considerations are given to personal protective equipment, viral testing, and alternatives. IMPLICATIONS FOR PRACTICE: Otolaryngologists worldwide must be aware of these considerations to provide safe patient care without undue risk to themselves or their hospital coworkers.


title: Inferring Timing of Infection Using Within-host SARS-CoV-2 Infection Dynamics Model: Are "Imported Cases" Truly Imported?

text: Importance: Although the COVID-19 epidemic in some countries such as China are in the last phase by large effort for containment of the disease, another outbreaks can occur because huge susceptible population remains. Further, there remain countries in the early phase of outbreak with zero or limited number of cases in southern hemisphere countries. In those countries at risk of future outbreak, ascertaining whether cases are imported or the result of local secondary transmission is important for government to shape appropriate public health strategies. Objective: To develop a method to estimate timing of infection establishment, which helps differentiate imported and autochthonous cases. Design, Setting and Participants: Of the first 18 cases reported in Singapore, 12 were used in our study (1 case with insufficient data and 5 on anti-viral treatment were excluded from the analysis). The viral load data from these initial cases considered imported due to their travel history to Wuhan were analyzed. Another viral load data from 3 cases reported from Zhuhai, China, for whom exposed day were known, were also analyzed to determine the viral load threshold for infection establishment. Exposures: SARS-CoV-2 infection confirmed by the polymerase-chain-reaction (PCR) test. Main Outcomes and Measures: The timing of infection establishment of each case was assessed by analysing viral load data after symptom onset using a within-host viral dynamics model for SARS-CoV-2. Estimated timing of infection will indicate whether cases are imported or autochthonous transmission within Singapore. Results: Six among the 12 cases were clearly imported cases, whereas we could not rule out the possibility of secondary transmission for the rest of 6 cases, which collectively evidenced ongoing transmission in Singapore. For the 6 cases who could be the results of secondary transmission, further investigation to identify the source of infection within Singapore should be warranted (i.e., contact tracing). Conclusions and Relevance: In an early phase of outbreak due to entrance or re-entrance of the virus to countries/communities, collecting viral load data over time from cases from symptom onset is highly recommended, because viral load data are valuable to infer the timing of infection and distinguish between imported cases and ongoing local transmission.


title: Knowledge system analysis on emergency management of public health emergencies

text: The Coronavirus Disease 2019 (COVID-19) infectious pneumonia pandemic highlights the importance of emergency management of public health emergencies (EMPHE). This paper addresses the challenge of building a knowledge system for EMPHE research that may contribute to understand the spatial and temporal characteristics of knowledge distribution, research status, cutting-edge research and development trends, and helps to identify promising research topics and guide research and practice of EMPHE. Based on the Web of Science, this paper retrieves 1467 articles about EMPHE published from 2010 to date. Then, based on high-frequency keywords, we use CiteSpace to analyze their knowledge co-occurrence network, clustering network and knowledge evolution. Furthermore, we summarize the features and gaps in EMPHE research, providing references for future research directions. Based on the above analysis, this work constructs a knowledge system about EMPHE research, providing a comprehensive visual summary of the existing research in the field of EMPHE, with the aim to guide future research and practice.


title: Rapid adaptation of SARS-CoV-2 in BALB/c mice: Novel mouse model for vaccine efficacy

text: Coronavirus disease 2019 (COVID-19) threatens global public health and economy. In order to develop safe and effective vaccines, suitable animal models must be established. Here we report the rapid adaption of SARS-CoV-2 in BALB/c mice, based on which a convenient, economical and effective animal model was developed. Specifically, we found that mouse-adapted SARS-CoV-2 at passage 6 (MACSp6) efficiently infected both aged and young wild-type BALB/c mice, resulting in moderate pneumonia as well as inflammatory responses. The elevated infectivity of MACSp6 in mice could be attributed to the substitution of a key residue (N501Y) in the receptorbinding domain (RBD). Using this novel animal model, we further evaluated the in vivo protective efficacy of an RBD-based SARS-CoV-2 subunit vaccine, which elicited highly potent neutralizing antibodies and conferred full protection against SARS-CoV-2 MACSp6 challenge. This novel mouse model is convenient and effective in evaluating the in vivo protective efficacy of SARS-CoV-2 vaccine. Summary This study describes a unique mouse model for SARS-CoV-2 infection and confirms protective efficacy of a SARS-CoV-2 RBD subunit vaccine.


title: Resilient SARS-CoV-2 diagnostics workflows including viral heat inactivation

text: There is a worldwide shortage of reagents to perform detection of SARS-2. Many clinical diagnostic laboratories rely on commercial platforms that provide integrated end-to-end solutions. While this provides established robust pipelines, there is a clear bottleneck in the supply of reagents given the current situation of extraordinary high demand. Some laboratories resort to implementing kit-free handling procedures, but many other small laboratories will not have the capacity to develop those and/or will perform manual handling of their samples. In order to provide multiple workflows for SARS-CoV-2 nucleic acid detection we compared several commercially available RNA extraction methods: QIAamp Viral RNA Mini Kit (QIAgen), the recently developed RNAdvance Blood (Beckman) and Mag-Bind Viral DNA/RNA 96 Kit (Omega Bio-tek). We also compared different 1-step RT-qPCR Master Mix brands: TaqMan™ Fast Virus 1-Step Master Mix (ThermoFisher Scientific), qPCRBIO Probe 1-Step Go Lo-ROX (PCR Biosystems) and Luna® Universal Probe One-Step RT-qPCR Kit (NEB). We used the Centre for Disease Control (CDC) recommended primers that detect two regions of the viral N gene as well as those that detect the RdRP gene region as per Public Health England (PHE) guidelines (Charite/WHO/PHE). Our data show that the RNA extraction methods provide similar results. Amongst the qPCR reagents tested, TaqMan™ Fast Virus 1-Step Master Mix and Luna® Universal Probe One-Step RT-qPCR Kit proved most sensitive. The N1 and N2 primer-probes provide a more reliable detection than the RdRP-SARSr primer-probe set, particularly in samples with low viral titres. Importantly, we have implemented a protocol using heat inactivation and demonstrate that it has minimal impact on the sensitivity of the qPCR in clinical samples - potentially making SARS-CoV-2 testing portable to settings that do not have CL-3 facilities.


title: Reset redux: possible evolutionary pathways towards the transformation of tourism in a COVID-19 world

text: With international arrivals surpassing 1.5 billion for the first time in 2019 the long-term evolution of tourism demonstrates prolific path dependence with a decade of growth since the global financial crisis. This latest period of unfettered international tourism development has come to an abrupt end as the impact of COVID-19 has brought the sector to a near standstill. As the world grapples with the realities of the global pandemic there is an opportunity to rethink exactly what tourism will look like for the decades ahead. Key concepts in evolutionary economic geography, especially path dependence/creation and institutional inertia/innovation, show variations in pathways for travel and tourism in a COVID-19 world. A path that leads to transformation in tourism can be realized if sufficient institutional innovation occurs on both the demand and supply side of tourism that can foster the emergence of new paths. COVID-19 presents a once in a generation opportunity where the institutional pump is primed for transformation. Whether that leads to a radical transformation of the tourism sector remains to be seen, but the imprint it will leave on both the demand and supply of tourism will have long-term, incremental impacts for years to come and ultimately move us closer towards the transformation of tourism.


title: Coatings and COVID-19

text: Traditionally, paint and coatings products have played a vital role in protecting consumers’ assets Whether it is a home, automobile, airplane, or electronic device, paints and coatings protect the products many use every day from corrosion, scratches, wear and tear, and stains In the midst of the novel coronavirus pandemic, the word protect is taking on even greater significance As we navigate these unprecedented times together, we are all focused on protecting the health and well-being of our families, colleagues, and friends Health-care workers, frontline responders, and scientists in the pharmaceutical and biotech industries are working tirelessly to fight this devastating pandemic and develop life-saving treatments and vaccines Now more than ever, they need our support And there are many other essential industries that also provide important products and services people count on The coatings industry continues to support frontline workers who are putting their own safety and health at risk every day The coatings industry is making sure that it manufactures and applies essential coatings—such as antibacterial-protected powder designed to inhibit the growth of bacteria—on surfaces and on medical devices and equipment, such as ventilators and vital sign monitors Coatings enable the protective performance of devices and equipment, ensuring that they work as intended and, ultimately, protect health-care workers and their patients Coatings also play a role in protecting temporary hospital installations and drive-through coronavirus testing facilities


title: Risk assessment of the overseas imported COVID-19 of ocean-going ships based on AIS and infection data

text: Preventing and controlling the risk of importing the coronavirus disease (COVID-19) has rapidly become a major concern. In addition to air freight, ocean-going ships play a non-negligible role in spreading COVID-19 due to frequent visits to countries with infected populations. This research introduces a method to dynamically assess the infection risk of ships based on a datadriven approach. It automatically identifies the ports and countries these ships approach based on their Automatic Identification Systems (AIS) data and a spatio-temporal density-based spatial clustering of applications with noise (ST-DBSCAN) algorithm. We derive daily and 14 day cumulative ship exposure indexes based on a series of country-based indices, such as population density, cumulative confirmed cases, and increased rate of confirmed cases. These indexes are classified into high-, middle-, and low-risk levels that are then coded as red, yellow, and green according to the health Quick Response (QR) code based on the reference exposure index of Wuhan on April 8, 2020. This method was applied to a real container ship deployed along a Eurasian route. The results showed that the proposed method can trace ship infection risk and provide a decision support mechanism to prevent and control overseas imported COVID-19 cases from international shipping.