title: A novel antiviral formulation inhibits a range of enveloped viruses

text: Some free fatty acids derived from milk and vegetable oils are known to have potent antiviral and antibacterial properties. However, therapeutic applications of short to medium chain fatty acids are limited by physical characteristics such as immiscibility in aqueous solutions. We evaluated a novel proprietary formulation based on an emulsion of short chain caprylic acid, ViroSAL, for its ability to inhibit a range of viral infections in vitro and in vivo. In vitro, ViroSAL inhibited the enveloped viruses Epstein-Barr, measles, herpes simplex, Zika and orf parapoxvirus, together with Ebola, Lassa, vesicular stomatitis and SARS-CoV-1 pseudoviruses, in a concentration- and time-dependent manner. Evaluation of the components of ViroSAL revealed that caprylic acid was the main antiviral component; however, the ViroSAL formulation significantly inhibited viral entry compared with caprylic acid alone. In vivo, ViroSAL significantly inhibited Zika and Semliki Forest Virus replication in mice following the inoculation of these viruses into mosquito bite sites. In agreement with studies investigating other free fatty acids, ViroSAL had no effect on norovirus, a non-enveloped virus, indicating that its mechanism of action may be via surfactant disruption of the viral envelope. We have identified a novel antiviral formulation that is of great interest for prevention and/or treatment of a broad range of enveloped viruses.


title: Evidence of the Recombinant Origin and Ongoing Mutations in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

text: The recent global outbreak of viral pneumonia designated as Coronavirus Disease 2019 (COVID-19) by coronavirus (SARS-CoV-2) has threatened global public health and urged to investigate its source. Whole genome analysis of SARS-CoV-2 revealed ~96% genomic similarity with bat CoV (RaTG13) and clustered together in phylogenetic tree. Furthermore, RaTGl3 also showed 97.43% spike protein similarity with SARS-CoV-2 suggesting that RaTGl3 is the closest strain. However, RBD and key amino acid residues supposed to be crucial for human-to-human and cross-species transmission are homologues between SARS-CoV-2 and pangolin CoVs. These results from our analysis suggest that SARS-CoV-2 is a recombinant virus of bat and pangolin CoVs. Moreover, this study also reports mutations in coding regions of 125 SARS-CoV-2 genomes signifying its aptitude for evolution. In short, our findings propose that homologous recombination has been occurred between bat and pangolin CoVs that triggered cross-species transmission and emergence of SARS-CoV-2, and, during the ongoing outbreak, SARS-CoV-2 is still evolving for its adaptability.


Infodemic and Risk Communication in the Era of CoV-19


title: The challenges of deploying artificial intelligence models in a rapidly evolving pandemic

text: The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus 2, emerged into a world being rapidly transformed by artificial intelligence (AI) based on big data, computational power and neural networks. The gaze of these networks has in recent years turned increasingly towards applications in healthcare. It was perhaps inevitable that COVID-19, a global disease propagating health and economic devastation, should capture the attention and resources of the world's computer scientists in academia and industry. The potential for AI to support the response to the pandemic has been proposed across a wide range of clinical and societal challenges, including disease forecasting, surveillance and antiviral drug discovery. This is likely to continue as the impact of the pandemic unfolds on the world's people, industries and economy but a surprising observation on the current pandemic has been the limited impact AI has had to date in the management of COVID-19. This correspondence focuses on exploring potential reasons behind the lack of successful adoption of AI models developed for COVID-19 diagnosis and prognosis, in front-line healthcare services. We highlight the moving clinical needs that models have had to address at different stages of the epidemic, and explain the importance of translating models to reflect local healthcare environments. We argue that both basic and applied research are essential to accelerate the potential of AI models, and this is particularly so during a rapidly evolving pandemic. This perspective on the response to COVID-19, may provide a glimpse into how the global scientific community should react to combat future disease outbreaks more effectively.


COVID-19 & Leadership


title: The effect of a national lockdown in response to COVID-19 pandemic on the prevalence of clinical symptoms in the population

text: SARS-CoV-2, a novel coronavirus and the cause of COVID-19, was isolated in December 2019 and has since been declared a pandemic by the World Health Organization (WHO). The vast and rapid spread of COVID-19 calls for immediate action from policy-makers and in many countries, various lockdown measures were implemented. Here, we utilized nationwide surveys that assess COVID-19 associated symptoms to analyse the effect of the lockdown policy in Israel on the prevalence of clinical symptoms in the population. Daily symptom surveys were distributed online and included fever, respiratory symptoms, gastrointestinal symptoms, anosmia and Ageusia. A total of 1,003,298 surveys were filled out to date. We used a single measure of symptoms, Symptoms Ratio (SR), defined as a weighted mean of symptoms found to be prevalent in COVID-19 patients. Notably, following severe lockdown measures, we found that between March 15 and April 22, the mean SR sharply declined by 78.9%, as did every individual symptom, including our most common symptoms of cough and rhinorrhea or nasal congestion, which decreased from 14.5% and 13.8% of the survey responders, respectively, to 2.4% and 2.5%. We also observed reduction in symptoms separately in the vast majority of cities in Israel. Overall, these results demonstrate a profound decrease in a variety of clinical symptoms following the implementation of a lockdown in Israel. As our survey symptoms are not specific to COVID-19 infection, this effect likely represents an overall nationwide reduction in the prevalence of infectious diseases, including COVID-19. This quantification may be of major interest for COVID-19 pandemic, as many countries consider implementation of lockdown strategies.


title: Map of SARS-CoV-2 spike epitopes not shielded by glycans

text: The severity of the COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, calls for the urgent development of a vaccine. The primary immunological target is the SARS-CoV-2 spike (S) protein. S is exposed on the viral surface to mediate viral entry into the host cell. To identify possible antibody binding sites not shielded by glycans, we performed multi-microsecond molecular dynamics simulations of a 4.1 million atom system containing a patch of viral membrane with four full-length, fully glycosylated and palmitoylated S proteins. By mapping steric accessibility, structural rigidity, sequence conservation and generic antibody binding signatures, we recover known epitopes on S and reveal promising epitope candidates for vaccine development. We find that the extensive and inherently flexible glycan coat shields a surface area larger than expected from static structures, highlighting the importance of structural dynamics in epitope mapping.


title: Functional and cognitive outcomes after COVID-19 delirium

text: Purpose To ascertain delirium prevalence and outcomes in COVID-19. Methods We conducted a point-prevalence study in a cohort of COVID-19 inpatients at University College Hospital. Delirium was defined by DSM-IV criteria. The primary outcome was all-cause mortality at 4 weeks; secondary outcomes were physical and cognitive function. Results In 71 patients, 31 (42%) had delirium, of which only 19 had been recognised by the clinical team. At 4 weeks, 20 (28%) had died, 26 (36%) were interviewed by telephone and 21 (30%) remained as inpatients. Physical function was substantially worse in people after delirium (-39 points on functional scale/166, 95% CI -92 to -21, p=0.01) (Table 2). Mean cognitive scores at follow-up were similar and delirium was not associated with mortality in this sample. Conclusions Our findings indicate that delirium is common, yet under-recognised. Delirium is associated with functional impairments in the medium-term.


title: O Group is a protective factor for COVID19 in Basque population

text: ABO blood groups have been related to COVID19 infection. ABO blood groups are slightly differently distributed in the populations and therefore these results should be replicated in the specific areas with a proper control population. In this work, we present data from 412 COVID19 patients and 17796 blood donors from Gipuzkoa, a region in Northern Spain. Our data shows the importance of group O as a protective factor.


title: Covid-19 and Population Age Structure

text: Epidemiological studies suggest that age distribution of a population has a non-trivial effect on how morbidity rates, mortality rates and case fatality rates (CFR) vary when there is an epidemic or pandemic. We look at the empirical evidence from a large cohort of countries to see the sensitivity of Covid-19 data to their respective median ages. The insights that emerge could be used to control for age structure effects while investigating other factors like cross-protection, co-morbidities, etc.


title: Maternal and perinatal characteristics and outcomes of pregnancies complicated with COVID-19 in Kuwait

text: Background: In late December of 2019, a novel coronavirus (SARS-CoV-2) was identified in the Chinese city Wuhan among a cluster of pneumonia patients. While it is known that pregnant women have reduced immunity and they are at risk for COVID-19 infection during the current pandemic, it is not clear if the disease manifestation would be different in pregnant women from non-pregnant women. Objectives: To describe the maternal and neonatal clinical features as well as outcome of pregnancies complicated with SARS-CoV-2 infection. Methods: In this retrospective national-based study, we analyzed the medical records of all SARS-CoV-2 positive pregnant patients and their neonates who were admitted to New-Jahra Hospital, Kuwait, between March 15th 2020 and May 31st 2020. The outcomes of pregnancies were assessed until the end date of follow-up (June 15th 2020). Results: A total of 185 pregnant women were enrolled with a median age of 31 years (interquartile range, IQR: 27.5-34), and median gestational age at diagnosis was 29 weeks (IQR: 18-34). The majority (88%) of the patients had mild symptoms, with fever (58%) being the most common presenting symptom followed by cough (50.6%). During the study period, 141 (76.2%) patients continued their pregnancy, 3 (1.6%) had a miscarriage, 1 (0.5%) had intrauterine fetal death and only 2 (1.1%) patients developed severe pneumonia and required intensive care. Most of the neonates were asymptomatic, and only 2 (5%) of them tested positive on day 5 by nasopharyngeal swab testing. Conclusion: Pregnant women do not appear to be at higher risk to the COVID-19 than the general population. The clinical features of pregnant women with SARS-CoV-2 infection were similar to those of the general population having SARS-CoV-2 infection. Favorable maternal and neonatal outcomes reinforce the existing evidence and may guide healthcare professionals in the management of pregnancies complicated with SARS-CoV-2 infection.


title: Gastrointestinal Infection Could Be New Focus for Coronavirus Diagnosis

text: It's not news to tell you that the coronavirus, known as COVID-19, is a worldwide pandemic. The initial outbreak of this novel virus in Wuhan in the Hubei province of China, first described in December 2019, has since moved on to being declared a pandemic by the World Health Organization. The classic description of COVID-19 is a respiratory illness that manifests with fever, dry cough, and dyspnea on exertion. However, gastrointestinal (GI) complication of COVID-19 is emerging as well. This was observed with similar viral respiratory illnesses, such as severe acute respiratory syndrome (SARS), which emerged in 2003, and the Middle East respiratory syndrome (MERS), which emerged in 2012. In a recently published, single-center case series of 138 consecutive hospitalized patients with confirmed COVID-19, investigators reported that approximately 10% of patients initially presented with GI symptoms, prior to the subsequent development of respiratory symptoms. Common and often very subtle symptoms included diarrhea, nausea, and abdominal pain, with a less common symptom being nonspecific GI illness. New studies are expanding our understanding of the possible fecal transmission of COVID-19. Assessment by polymerase chain reaction (PCR) has provided evidence of the virus in the stool and the oropharynx outside the nasopharynx and respiratory tract. Virus in the stool may be evident on presentation and last throughout the course of illness resolution for up to 12 days after the respiratory virus evidence is gone. In fact, in one of the most recent studies looking at 73 patients, approximately 24% remained positive in their stool for evidence of the virus, though not necessarily infection, after showing negative in respiratory samples. The Centers for Disease Control and Prevention (CDC) recommends that after two negative respiratory tests separated by ≥ 24 hours, patients can be dismissed from having transmissibility infection risk for COVID-19. The potential for fecal-oral transmission of COVID-19 needs to be strongly considered. Considering these cases and the lessons from SARS, many authors recommend that real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from feces should be performed routinely in SARS-CoV-2 patients.


title: Many shades of wrong: what governments do when they manipulate statistics

text: A considerable number of recent analyses report statistical evidence indicating that governments manipulate official macroeconomic indicators. Employing creative strategies to identify systematic biases in statistical outputs, these studies have shown that political manipulation of economic statistics does occur. But they have paid less attention to the question how official statistics are being manipulated. To shed light on the processes behind data manipulation, this article examines three recent high-profile cases in depth: Greece’s public deficit figures, controversies about Argentina’s inflation statistics, and the Brazilian “fiscal pedaling” scandal. We make two main contributions: first, macroeconomic indicators are much more ambiguous than it is commonly realized. Therefore, the line between accurate and manipulated data is more blurry than typical narratives about manipulation acknowledge. Second, in recognition of this ambiguity we introduce a typology distinguishing four types of manipulation: outright manipulation (type 1), politically motivated guesstimating (type 2), the opportunistic use of methodology space (type 3), and indicators-management through indirect means (type 4). The findings from our cases highlight that the politics of statistics do not revolve around “right” and “wrong” numbers. They are better understood as contestations about different shades of wrong.


title: Assessment of sample pooling for clinical SARS-CoV-2 testing

text: Accommodating large increases in sample workloads has presented one of the biggest challenges to clinical laboratories during the COVID-19 pandemic. Despite the implementation of new automated detection systems, and previous efficiencies such as barcoding, electronic data transfer and extensive robotics, throughput capacities have struggled to meet the demand. Sample pooling has been suggested as an additional strategy to further address this need. The greatest concern with this approach in a clinical setting is the potential for reduced sensitivity, particularly the risk of false negative results when weak positive samples are pooled. To investigate this possibility, detection rates in pooled samples were evaluated, with extensive assessment of pools containing weak positive specimens. Additionally, the frequency of occurrence of weak positive samples across ten weeks of the pandemic were reviewed. Weak positive specimens were detected in all five-sample pools but failed to be detected in four of the 24 nine-sample pools tested. Weak positive samples comprised an average 16.5% of the positive specimens tested during the pandemic thus far, slightly increasing in frequency during later weeks. Other aspects of the testing process should be considered, however, such as accessioning and reporting, which are not streamlined and may be complicated by pooling procedures. Therefore, the impact on the entire laboratory process needs to be carefully assessed prior to implementing such a strategy.


title: How well can we forecast the COVID-19 pandemic with curve fitting and recurrent neural networks?

text: Predictions of the COVID-19 pandemic in USA are compared using curve fitting and various recurrent neural networks (RNNs) including the standard long short-term memory (LSTM) RNN and 10 types of slim LSTM RNNs. The curve fitting method predicts the pandemic would end in early summer but the exact date and scale vary with the evolving data used for fitting. All LSTM RNNs result in short-term (8 to 10 days) predictions with comparable accuracies (smaller than 10 %) to curve fitting---they do not show advantage over curve fitting.


title: Chest X-Ray Has Poor Diagnostic Accuracy and Prognostic Significance in COVID-19: A Propensity Matched Database Study

text: Objectives: To identify the diagnostic accuracy of common imaging modalities, chest X-ray (CXR) and computed tomography (CT) for diagnosis of COVID-19 in the general emergency population in the UK and to find the association between imaging features and outcomes in these patients. Design: Retrospective analysis of electronic patient records Setting: Tertiary academic health science centre and designated centre for high consequence infectious diseases in London, UK. Participants: 1,198 patients who attended the emergency department with paired RT-PCR swabs for SARS-CoV 2 and CXR between 16th March and 16th April 2020 Main outcome measures: Sensitivity and specificity of CXR and CT for diagnosis of COVID-19 using the British Society of Thoracic Imaging reporting templates. Reference standard was any reverse transcriptase polymerase chain reaction (RT-PCR) positive naso-oropharyngeal swab within 30 days of attendance. Odds ratios of CXR in association with vital signs, laboratory values and 30-day outcomes were calculated. Results: Sensitivity and specificity of CXR for COVID-19 diagnosis were 0.56 (95% CI 0.51-0.60) and 0.60 (95% CI 0.54-0.65), respectively. For CT scans these were 0.85 (95% CI 0.79-0.90) and 0.50 (95% CI 0.41-0.60), respectively. This gave a statistically significant mean increase in sensitivity with CT compared with CXR, of 29% (95% CI 19%-38%, p<0.0001). Specificity was not significantly different between the two modalities. Chest X-ray findings were not statistically significantly or clinical meaningfully associated with vital signs, laboratory parameters or 30-day outcomes. Conclusions: Computed tomography has substantially improved diagnostic performance over CXR in COVID-19. CT should be strongly considered in the initial assessment for suspected COVID-19. This gives potential for increased sensitivity and considerably faster turnaround time, where capacity allows and balanced against excess radiation exposure risk.


title: Clinical Ordering Practices of the SARS-CoV-2 Antibody Test at a Large Academic Medical Center

text: Background: The novel severe acute respiratory coronavirus 2 (SARS-CoV-2) that causes COVID-19 originated in December 2019 and has now infected over 3 million people in the United States. In Spring of 2020, private laboratories and some hospitals began antibody testing despite lacking evidence-based guidance. Objective: To describe clinician-described indications for SARS-CoV-2 antibody testing, including cost implications, immediately following testing availability. Design: Retrospective chart review of patients who received antibody testing from May 14, 2020 to June 15, 2020. Setting: A large academic medical center, one of the first in the US to provide antibody testing capability to individual clinicians. Patients: 447 consecutive patients who received SARS-CoV-2 antibody testing. Measurements: Clinician-described indications for SARS-CoV-2 antibody testing, cost implications, and comparison with current expert-based guidance from the IDSA and CDC. Results: Of 444 individual antibody test results meeting inclusion criteria, the two most commonly described indications for ordering the antibody test, apart from public health epidemiology studies (n=223), were for patients with a now resolved COVID-19 compatible illness (n=105) with no previous molecular testing and in asymptomatic patients believed to have had a past exposure or contact with a person with COVID-19 compatible illness (n=60). The rate of positive SARS-CoV-2 antibody testing among those indications consistent with current IDSA and CDC guidance was 17% compared with 5% (p<0.0001) among those indications inconsistent with current IDSA and CDC guidance. Total cost estimates ranged from $57,720 to $97,680, of which 42% was for testing inconsistent with current expert-based guidance. Limitations: The duration of antibody response following infection is unclear and asymptomatic individuals may not develop a positive antibody response. Conclusions: Our findings demonstrate a dissociation between clinician described indications for testing and expert-based guidance and a significantly different rate of positive testing between these two groups. Clinical curiosity and patient preference appear to have played a significant role in testing decisions and substantially contributed to testing costs.


title: Deducing the N- and O- glycosylation profile of the spike protein of novel coronavirus SARS-CoV-2

text: The current emergence of the novel coronavirus pandemic caused by SARS-CoV-2 demands the development of new therapeutic strategies to prevent rapid progress of mortalities. The coronavirus spike (S) protein, which facilitates viral attachment, entry and membrane fusion is heavily glycosylated and plays a critical role in the elicitation of the host immune response. The spike protein is comprised of two protein subunits (S1 and S2), which together possess 22 potential N-glycosylation sites. Herein, we report the glycosylation mapping on spike protein subunits S1 and S2 expressed on human cells through high resolution mass spectrometry. We have characterized the quantitative N-glycosylation profile on spike protein and interestingly, observed unexpected O-glycosylation modifications on the receptor binding domain (RBD) of spike protein subunit S1. Even though O-glycosylation has been predicted on the spike protein of SARS-CoV-2, this is the first report of experimental data for both the site of O-glycosylation and identity of the O-glycans attached on the subunit S1. Our data on the N- and O-glycosylation is strengthened by extensive manual interpretation of each glycopeptide spectra in addition to using bioinformatics tools to confirm the complexity of glycosylation in the spike protein. The elucidation of the glycan repertoire on the spike protein provides insights into the viral binding studies and more importantly, propels research towards the development of a suitable vaccine candidate.


title: Expectations, Fears and Perceptions of doctors during Covid-19 Pandemic

text: OBJECTIVES: The aim of this study was to explore the expectations and fears faced by doctors during Covid-19 Pandemic. METHODS: This is a mixed method exploratory survey. A questionnaire exploring expectations of doctors from administration and seniors as well as their fears while working during pandemic, was developed on Google survey Forms. It included eight closed ended questions and four open ended questions. Data was collected through online Google survey Forms during month of March and April 2020. Doctors were approached through email and WhatsApp group. RESULTS: The mean age of participants was 33.58±4.21 years. Female 150(67.5%) and Male 72(32.4%) participated. 29(13.1%) Associate Professor, 34(15.3%) Assistant Professor, 56(25.2%) Senior Residents and 103(46.3%) residents, medical officers and house officers responded to the survey. 134(60.3%) doctors were working in hospitals which were not dealing with Covid-19. Fear included, infecting family members 177(79.7%), rapid spread of disease 140(63%), complications of disease 134(60.3%), becoming a carrier in 64(28.8%) and 62(27.9%) feared missing the diagnosis. More than 80% expected from seniors and administration, of providing PPE, facilitation, continue chain of supply of essential items, ensuring doctor safety, avoiding exposure of all doctors and keeping reserve workforce, limiting routine checkups, avoid panic and 20% had no expectations. CONCLUSION: It was concluded that doctors had their fears and perceptions regarding pandemic which need to be addressed while policy making. They fear wellbeing of their families and contacting Covid-19, if not provided proper PPE. Our study provides insight of expectations, fears and perceptions of our frontline which invariably gives insight of the views of healthcare workers.


title: Bioinformatics analysis and collection of protein post-translational modification sites in human viruses

text: In viruses, post-translational modifications (PTMs) are essential for their life cycle. Recognizing viral PTMs is very important for better understanding the mechanism of viral infections and finding potential drug targets. However, few studies have investigated the roles of viral PTMs in virus-human interactions using comprehensive viral PTM datasets. To fill this gap, firstly, we developed a viral post-translational modification database (VPTMdb) for collecting systematic information of viral PTM data. The VPTMdb contains 912 PTM sites that integrate 414 experimental-confirmed PTM sites with 98 proteins in 45 human viruses manually extracted from 162 publications and 498 PTMs extracted from UniProtKB/Swiss-Prot. Secondly, we investigated the viral PTM sequence motifs, the function of target human proteins, and characteristics of PTM protein domains. The results showed that (i) viral PTMs have the consensus motifs with human proteins in phosphorylation, SUMOylation and N-glycosylation. (ii) The function of human proteins that targeted by viral PTM proteins are related to protein targeting, translation, and localization. (iii) Viral PTMs are more likely to be enriched in protein domains. The findings should make an important contribution to the field of virus-human interaction. Moreover, we created a novel sequence-based classifier named VPTMpre to help users predict viral protein phosphorylation sites. Finally, an online web server was implemented for users to download viral protein PTM data and predict phosphorylation sites of interest. Author summary Post-translational modifications (PTMs) plays an important role in the regulation of viral proteins; However, due to the limitation of data sets, there has been no detailed investigation of viral protein PTMs characteristics. In this manuscript, we collected experimentally verified viral protein post-translational modification sites and analysed viral PTMs data from a bioinformatics perspective. Besides, we constructed a novel feature-based machine learning model for predicting phosphorylation site. This is the first study to explore the roles of viral protein modification in virus infection using computational methods. The valuable viral protein PTM data resource will provide new insights into virus-host interaction.


title: A Global Scale Estimate of Novel Coronavirus (COVID-19) Cases Using Extreme Value Distributions

text: The COVID 19 pandemic has created a global crisis and the governments are fighting rigorously to control the spread by imposing intervention measures and increasing the medical facilities. In order to tackle the crisis effectively we need to know the trajectories of number of the people infected (i.e. confirmed cases). Such information is crucial to government agencies for developing effective preparedness plans and strategies. We used a statistical modeling approach (extreme value distributions, EVDs) for projecting the future confirmed cases on a global scale. Using the 69 days data (from January 22, 2020 to March 30, 2020), the EVDs model predicted the number of confirmed cases from March 31, 2020 to April 9, 2020 (validation period) with an absolute percentage error < 15 % and then projected the number of confirmed cases until the end of June 2020. Also, we have quantified the uncertainty in the future projections due to the delay in reporting of the confirmed cases on a global scale. Based on the projections, we found that total confirmed cases would reach around 11.4 million globally by the end of June 2020.The USA may have 2.9 million number of confirmed cases followed by Spain(1.52 million) and Italy (1.28 million).


title: Evaluating the different control policies for COVID-19 between mainland China and European countries by a mathematical model in the confirmed cases

text: This study focuses on evaluating the different policies of controlling the outbreak of COVID-19 in mainland China and in some European countries. The study is based on mathematical model which is a modified susceptible-infected-recovered (SIR) model. The model takes death and recovery into consideration which in convenience is called the susceptible-infected-recovered-death (SIRD) model. The criterion for the recovered patients is assumed by COVID-19 nucleic acid testing negative. The mathematical model is constructed by retrospective study. Determination of the parameters in the model is based on the epidemic bulletin supplied by the Chinese Center for Disease Control and Prevention (CDC) and National Health Commission of the People's Republic of China (NHC) from Jan 16 2020 to Mar 5 2020. The data cover the date when the epidemic situation is reported and the data showed that the epidemic situation is almost under control in China. The mathematical model mainly simulates the active cases and the deaths during the outbreak of COVID-19. Then apply the mathematical model to simulate the epidemic situations in Italy and Spain, which are suffering the outbreak of COVID-19 in Europe. The determination of the parameters for the 2 European countries is based on the data supplied by Worldometers. By comparing the difference of the parameters based on the same mathematical model, it is possible to evaluate the different policies in different countries. It turns out that the relatively easing control policies might lead to rapid spread of the disease.


title: A mechanistic approach to predict the material removal rate in Ice Bonded Abrasive Polishing (IBAP)

text: Abstract The growing demand for ultrafine surface generation has forced the researchers to look for new methods of polishing that can guarantee both qualities as well as productivity. The existing polishing methods have several limitations such as bluntness of tool due to loading, metallurgical changes on the polished surface due to frictional heat generated at the interface, etc. These limitations have prompted the researchers to develop self-sharpening polishing tools. One such method is Ice Bonded Abrasive Polishing (IBAP) which uses frozen slurry for polishing, where ice serves as a matrix to hold the abrasives. Frictional heat produced at tool work interface causes the tool to melt and thus exposes fresh abrasives present in different layers. This paper attempts to interpret the mechanisms responsible for the ultrafine surface generation and then to develop an analytical model for estimating material removal. During polishing, the asperities on work surface experience variable force due to the changing condition of the tool with time. Initially, the first layer of rigid ice with fixed abrasives interacts with the work surface, making it as a solid-solid interaction. Molten state of ice behaves as semisolid and leads to slurry formation afterward. Therefore, the work surface will experience two-body and three-body interactions simultaneously. The proposed model implements the concepts of contact mechanics for predicting material removal from the work surface and finally, the effectiveness of the model has been validated with experimental results.


Management of hospitalized patients with pulmonary arterial hypertension and COVID-19 infection


title: Signature of State measures on the COVID-19 Pandemic in China, Italy, and USA

text: We show the dynamics of COVID-19 outbreak in Italy and USA, in comparison with China, and the early response of the countries. Our mathematical techniques makes it possible to calculate the rate of growth of the cases efficiently, and provides a good understanding of future trends in Italy and USA. The evolution of the real time data makes it possible to analyse the suitability of steps taken to eradicate the pandemic by the countries. We compare the day to day development of the coronavirus cases in Italy and USA, that keeping in view the population pyramid and the population density, leads us to understand possible difference in the number of effected population.


title: Identification of Vulnerable Populations and Areas at Higher Risk of COVID-19 Related Mortality in the U.S.

text: Background The role of health-related disparities including sociodemographic, environmental, and critical care capacity in the COVID-19 pandemic are poorly understood. In the present study, we characterized vulnerable populations located in areas at higher risk of COVID-19 related mortality and low critical healthcare capacity in the U.S. Methods Using Bayesian multilevel analysis and small area disease risk mapping, we assessed the spatial variation of COVID-19 related mortality risk for the U.S. in relation with healthcare disparities including race, ethnicity, poverty, air quality, and critical healthcare capacity. Results Overall, highly populated, regional air hub areas, and minorities had an increased risk of COVID-19 related mortality. We found that with an increase of only 1 ug/m3 in long term PM2.5 exposure, the COVID-19 mortality rate increased by 13%. Counties with major air hubs had 18% increase in COVID-19 related death compared to counties with no airport connectivity. Sixty-eight percent of the counties with high COVID-19 related mortality risk were also counties with lower critical care capacity than national average. These counties were primary located at the North- and South-Eastern regions of the country. Conclusion The existing disparity in health and environmental risk factors that exacerbate the COVID-19 related mortality, along with the regional healthcare capacity, determine the vulnerability of populations to COVID-19 related mortality. The results from this study can be used to guide the development of strategies for the identification and targeting preventive strategies in vulnerable populations with a higher proportion of minority groups living in areas with poor air quality and low healthcare capacity.


title: Radiotherapy department reorganization during the COVD-19 outbreak: keys to securing staff and patients during the first weeks of the crisis and impact on radiotherapy practice from a single institution experience.

text: INTRODUCTION: During the first weeks of coronavirus 2019 (COVID-19) outbreak in France, it was necessary to clearly define the organizational priorities in the radiotherapy (RT) departments. In this report, we focus on the urgent measures taken to reduce risk for our staff and for patients by reducing the number of patients on treatment. MATERIALS AND METHODS: We reviewed the fractionation schemes for all patients in our department, including those on treatment and those soon to start treatment. Our goal was to decrease the number of patients coming daily to the hospital for RT and adapt our human resources to continue patients’ care in the department and help to cover understaffed COVID-19 sectors of the hospital. RESULTS: We identified 50 patients who were on treatment (n=6) or were going to start radiation soon as the CT scan simulation has been performed (n=41) and those for whom the CT scan was pending (n=3). The majority were women (64%) treated for breast cancer (54%). RT was delayed for 22 (44%). The majority were offered hormonal therapy as “waiting therapy”. Hypofractionation was considered in 21 (42%) patients with mainly breast cancer patients (18/21, 86%). The number of courses initially planned and re-planned due to the COVID-19 outbreak during the period March 15-May 31, 2020, were 1383 and 683, which represented a reduction of 50% (including delayed sessions) that allowed our reorganization process. CONCLUSION: To conserve resources during the pandemic, we successfully cut down on the number of patients on treatment in a proactive fashion and adapted our organization to minimize the risk of COVID-19 contaminations. Departments across the world may benefit from this same approach.


title: Global COVID-19 transmission rate is influenced by precipitation seasonality and the speed of climate temperature warming

text: The novel coronavirus disease 2019 (COVID-19) became a rapidly spreading worldwide epidemic; thus, it is a global priority to reduce the speed of the epidemic spreading. Several studies predicted that high temperature and humidity could reduce COVID-19 transmission. However, exceptions exist to this observation, further thorough examinations are thus needed for their confirmation. In this study, therefore, we used a global dataset of COVID-19 cases and global climate databases and comprehensively investigated how climate parameters could contribute to the growth rate of COVID-19 cases while statistically controlling for potential confounding effects using spatial analysis. We also confirmed that the growth rate decreased with the temperature; however, the growth rate was affected by precipitation seasonality and warming velocity rather than temperature. In particular, a lower growth rate was observed for a higher precipitation seasonality and lower warming velocity. These effects were independent of population density, human life quality, and travel restrictions. The results indicate that the temperature effect is less important compared to these intrinsic climate characteristics, which might thus be useful for explaining the exceptions. However, the contributions of the climate parameters to the growth rate were moderate; rather, the contribution of travel restrictions in each country was more significant. Although our findings are preliminary owing to data-analysis limitations, they may be helpful when predicting COVID-19 transmission.


title: Health and economic impact of covid-19: Mapping the consequences of a pandemic in malaysia

text: The World Health Organization (WHO) has termed the novel coronavirus infection a pandemic based on number of confirmed cases in more than 195 countries and with risk of further spread. The infection has had drastic impact on global trade and stock markets. The Malaysian authorities realised the need to ensure availability of health resources and facilities in the country so that the healthcare professionals could treat serious cases on priority basis. Steps have been taken to ensure that health facilities are not overwhelmed with cases and do not become the source of virus spread to other healthcare staff and patients.


title: SARS-CoV-2 virus culture from the upper respiratory tract: Correlation with viral load, subgenomic viral RNA and duration of illness.

text: In 68 respiratory specimens from a cohort of 35 COVID-19 patients, 32 of them with mild disease, we found SARS coronavirus-2 virus culture and sub-genomic RNA was rarely detectable beyond 8 days after onset of illness although virus RNA by RT-PCR remained detectable for many weeks.


title: Effective Screening of SARS-CoV-2 Neutralizing Antibodies in Patient Serum using Lentivirus Particles Pseudotyped with SARS-CoV-2 Spike Glycoprotein

text: Pseuodotyped particles have significant importance and use in virology as tools for studying the biology of highly pathogenic viruses in a lower biosafety environment. The biological, chemical, and serological studies of the recently emerged SARS-CoV-2 will be greatly aided by the development and optimization of a suitable pseudotyping system. Here, we pseudotyped the SARS-CoV-2 Spike glycoprotein (SPG) on a retroviral (MMLV) as well as a third generation lentiviral (pLV) vector and tested the transduction efficiency in several mammalian cell lines expressing SARS-CoV-2 receptor hACE2. While MMLV pseudotyped the vesicular stomatitis virus G glycoprotein (VSV-G) efficiently, it could not pseudotype SPG. In contrast, pLV pseudotyped both glycoproteins efficiently; however, much higher titers of pLV-G particles were produced. Among all the tested mammalian cells, 293Ts expressing hACE2 were most efficiently transduced using the pLV-S system. The pLV-S particles were efficiently neutralized by diluted serum (>:640) from a recently recovered COVID-19 patient who showed high SARS-CoV-2 specific IgM and IgG levels. In summary, pLV-S pseudotyped virus provides a valid screening tool for the presence of anti SARS-CoV-2 specific neutralizing antibodies in convalescent patient serum.


title: The fate of SARS-CoV-2 in wastewater treatment plants points out the sludge line as a suitable spot for incidence monitoring

text: SARS-CoV-2 genetic material is detectable in the faeces of a considerable part of COVID-19 cases and hence, in the urban wastewater. This fact was confirmed early during the spread of the COVID-19 pandemic and prompted several studies that proposed monitoring its incidence by wastewater. This paper studies the fate of SARS-CoV-2 genetic material in wastewater treatment plants using RT-qPCR with a two-fold goal: i) to check the safety of the water effluent and also of the sludge produced and ii) based on the understanding of the virus particles fate, to identify the most suitable spots for detecting the incidence of COVID-19 and monitor its evolution. On the grounds of the affinity of enveloped virus towards biosolids, we hypothesized that the sludge line acts as a concentrator of SARS-CoV-2 genetic material. Sampling several spots in primary, secondary and sludge treatment at the Ourense (Spain) WWTP showed that, in effect, most of SARS-CoV-2 particles cannot be detected in the water effluent as they are retained by the sludge line. We identified the sludge thickener as a suitable spot for detecting SARS-CoV-2 particles thanks to its higher solids concentration (more virus particles) and longer residence time (less sensitive to dilution caused by precipitation). Although more studies will be needed for confirmation, these results contribute to clarify the role of WWTPs in COVID-19 mitigation.


title: The impact of traffic isolation in Wuhan on the spread of 2019-nCov

text: The 2019-nCoV outbreak occurred near the Chinese Spring Festival transport period in Wuhan. As an important transportation center, the migration of Wuhan accelerated the spread of 2019-nCoV across mainland China. Based on the cumulative Baidu migration index (CBMI), we first analyzed the proportion of Wuhan's migrant population to other cities. Our results confirm that there is a significant correlation between the export population of Wuhan and reported cases in various regions. We subsequently found that the mortality rate in Hubei Province was much higher than that in other regions of mainland China, while the investigation of potential cases in Wuhan was far behind other provinces in Mainland China, which indicates the effectiveness of early isolation.


title: ddPCR: a more sensitive and accurate tool for SARS-CoV-2 detection in low viral load specimens

text: Background: Real-Time PCR (RT-PCR) is widely used as the gold standard for clinical detection of SARS-CoV-2. However, due to the low viral load in patient throat and the limitation of RT-PCR, significant numbers of false negative reports are inevitable, which should not be ignored. Methods: We explored the feasibility of droplet digital PCR (ddPCR) to detect SARS-CoV-2 from 57 clinical pharyngeal swab samples and compared with RT-PCR in terms of the sensitivity and accuracy. Among 57 samples, all of which were reported as negative nucleic acid by officially approved clinical RT-PCR detection, 43 samples were collected from suspected patients with fever in clinic, and 14 were from supposed convalescents who were about to discharge after treatment. The experiment was double-blind. Results: The lower limit of detection of the optimized ddPCR is at least 500 times lower than that of RT-PCR. The overall accuracy of ddPCR for clinical detection is 94.3 %. 33 out of 35 negative pharyngeal swab samples checked by RT-PCR were correctly judged by ddPCR based on the follow-up investigation. In addition, 9 out of 14 (64.2 %) supposed convalescents with negative nucleic acid test twice by RT-PCR were positive by ddPCR detection. Conclusions: ddPCR shows superiority for clinical detection of SARS-CoV-2 to reduce the false negatives, which could be a powerful complement to the current standard RT-PCR. Before the ddPCR to be approved for diagnosis, the current clinical practice that the convalescent continues to be quarantined for 2 weeks is reasonable and necessary.


title: COVID-19 Antibody Test / Vaccination Certification: There's an app for that

text: Goal: As the Coronavirus Pandemic of 2019/2020 unfolds, a COVID-19 'Immunity Passport' has been mooted as a way to enable individuals to return back to work. While the quality of antibody testing, the availability of vaccines, and the likelihood of even attaining COVID-19 immunity continue to be researched, we address the issues involved in providing tamper-proof and privacy-preserving certification for test results and vaccinations. Methods: We developed a prototype mobile phone app and requisite decentralized server architecture that facilitates instant verification of tamper-proof test results. Personally identifiable information is only stored at the user's discretion, and the app allows the end-user selectively to present only the specific test result with no other personal information revealed. The architecture, designed for scalability, relies upon (a) the 2019 World Wide Web Consortium standard called 'Verifiable Credentials', (b) Tim Berners-Lee's decentralized personal data platform 'Solid', and (c) a Consortium Ethereum-based blockchain. Results: Our mobile phone app and decentralized server architecture enable the mixture of verifiability and privacy in a manner derived from public/private key pairs and digital signatures, generalized to avoid restrictive ownership of sensitive digital keys and/or data. Benchmark performance tests show it to scale linearly in the worst case, as significant processing is done locally on each app. For the test certificate Holder, Issuer (e.g. healthcare staff, pharmacy) and Verifier (e.g. employer), it is 'just another app' which takes only minutes to use. Conclusions: The app and decentralized server architecture offer a prototype proof of concept that is readily scalable, applicable generically, and in effect 'waiting in the wings' for the biological issues, plus key ethical issues raised in the discussion section, to be resolved.


title: Girls gone wild: Social isolation induces hyperactivity and exploration in aged female mice

text: The likelihood of experiencing social isolation increases later in life, particularly for females. It remains unknown how late-life social isolation impacts cognition and affective behavior in aged mice. We assessed the impact of late-life social isolation in 18-month old female mice. One month of single-housing did not lead to robust depressive-like symptomology, altered social interaction behavior, or sensitivity to context fear acquisition or memory. Rather, isolation increased hyperactivity and exploration, and reduced anxiety-like behavior in the open field and elevated plus maze, findings that have been similarly observed in young female and male mice following early-life isolation. These findings suggest that hyperactivity is a robust behavior following social isolation across the lifespan.


title: In vivo demonstration of microvascular thrombosis in severe Covid-19

text: Several autopsies studies showed the presence of microthrombi in the pulmonary circulation of the severe COVID-19. The major limitation of these investigations is that the autopsy provided static information. Some of these alterations could be secondary to the disseminated intravascular coagulation (DIC) observed as the final common pathway of the multisystem organ failure exhibited in the critical patient. We report the preliminary results of an in vivo evaluation of the sublingual microcirculation in thirteen patients with severe COVID-19 requiring mechanical ventilation at the beginning of the hospitalization. They did not have any laboratorial DIC evidence. We observed multiple filling defects moving within the sublingual microvessels indicative of microthrombi in 11 (85%) patients. This is the first imaging documentation of microvascular thrombosis in living patients with severe COVID-19. The clinical relevance of microvascular thrombosis in this disease requires further research.


title: Enhancing the Antiviral Efficacy of RNA-Dependent RNA Polymerase Inhibition by Combination with Modulators of Pyrimidine Metabolism

text: Genome-wide analysis of the mode of action of GSK983, a potent antiviral agent, led to the identification of dihydroorotate dehydrogenase (DHODH) as its target, along with the discovery that knockdown of genes in pyrimidine salvage pathways sensitized cells to GSK983. Because GSK983 is an ineffective antiviral in the presence of physiological uridine concentrations, we explored combining GSK983 with pyrimidine salvage inhibitors. We synthesized and evaluated analogs of cyclopentenyl uracil (CPU), an inhibitor of uridine salvage. We found that CPU was efficiently converted into its triphosphates in cells. When combined with GSK983, it led to large drops in cellular UTP and CTP pools. Consequently, CPU-GSK983 suppressed dengue virus replication in the presence of physiological concentrations of uridine. In addition, the CPU-GSK983 combination markedly enhanced the effect of RNA-dependent RNA polymerase (RdRp) inhibition on viral genome infection. Our findings highlight a new host-targeting strategy for potentiating the antiviral activities of RdRp inhibitors.


title: Enhanced Hybrid Copper Conductive Ink for Low Power Selective Laser Sintering

text: Abstract Copper conductive ink has great potential as an electrode material for flexible electronics due to its low-cost relative to silver conductive ink while having comparable electrical conductivity. The process of fabricating anti-oxidation hybrid copper conductive ink, however, results in an increase of required sintering energy; a high sintering temperature is disadvantageous due to the possibility of thermally damaging the substrate. In this study, selective laser sintering of new hybrid ink compositions was investigated by varying laser intensities and comparatively analyzing the resulting electrical conductivity. Then, the thermal behavior of fabricated inks during the sintering process was studied using experimental and numerical approaches. A finite element model was developed to simulate the laser heat flux and irradiation paths on the ink. Finally, the obtained results of the thermal profile were verified experimentally.


Traditional Chinese medicine for novel coronavirus pneumonia treatment: main force or supplement?


title: Effects of sample processing modes on high-throughput sequencing of coronavirus whole genome/ 不同样本测序前处理方案对冠状病毒基因组高通量测序结果的影响

text: Objective: To study the effects of different pre-sequencing sample processing modes on the results of whole genome sequencing with high-throughput sequencing (HTS) by taking the largest RNA virus (human coronavirus, HCoV) as the representative. Methods: Cell-cultured human coronavirus HCoV-OC43 strains were used as the representative samples and divided into different groups based on pre-sequencing processing modes as follows: untreated group, DNase and RNase treatment before nucleic acid extraction group, DNase treatment after nucleic acid extraction group, and DNase and RNase treatment before nucleic acid extraction and DNase treatment after nucleic acid extraction group. Nucleic acid samples of each group were analyzed by direct RNA sequencing (without amplification) and DNA sequencing after sequence independent single primer amplification (SISPA), respectively. Results: No significant difference in viral genome coverage rates was observed between different groups. The highest genome coverage and sequencing accuracy were obtained in DNase treatment after nucleic acid extraction group by direct RNA sequencing, and the ratio of viral reads and the sequencing depth of each locus were effectively improved by SISPA amplification. Conclusions: This study provided an optimized technical strategy for whole genome sequencing of RNA viruses such as coronavirus.


title: A Noel Intervention Recurrent autoencoder for real time forecasting and non-pharmaceutical intervention selection to curb the spread of Covid-19 in the world

text: ABSTRACT Objective: Develop the AI and casual inference-inspired methods for forecasting and evaluating the effects of public health interventions on curbing the spread of Covid-19. Methods: We developed recurrent neural network (RNN) for modeling the transmission dynamics of the epidemics and Counterfactual-RNN (CRNN) for evaluating and exploring public health intervention strategies to slow down the spread of Covid-19 worldwide. We applied the developed methods to real-time forecasting the confirmed cases of Covid-19 across the world. The data were collected from January 22 to April 18, 2020 by John Hopkins Coronavirus Resource Center (https://coronavirus.jhu.edu/MAP.HTML). Results: The average errors of 1-step to 10-step forecasting were 2.9%. In the absence of a COVID-19 vaccine, we evaluated the potential effects of a number of public health measures. We found that the estimated peak number of new cases and cumulative cases, and the maximum number of cumulative cases worldwide with one week later additional intervention were reduced to 103,872, 2,104,800, and 2,271,648, respectively. The estimated total peak number of new cases and cumulative cases would be the same as the above and the maximum number of cumulative cases would be 3,864,872 in the world with 3 week later additional intervention. Duration time of the Covid-19 spread would be increased from 91 days to 123 days. Our estimation results showed that we were in the eve of stopping the spread of COVID-19 worldwide. However, we observed that transmission would quickly rebound if interventions were relaxed. Conclusions: The accuracy of the AI-based methods for forecasting the trajectory of Covid-19 was high. The AI and causal inference-inspired methods are a powerful tool for helping public health planning and policymaking. We concluded that the spread of COVID-19 would be stopped very soon.


Speech therapy, breastfeeding and COVID-19: Information to speech therapist


title: Hand Washing Compliance and COVID-19: A Non-Participatory Observational Study among Hospital Visitors

text: Background: Hand washing remains a key measure for intercepting the dispatch of the Coronavirus disease (COVID-19). However, hand washing must be perpetuated properly using soap and water for at least 20 seconds. In response to the current COVID-19 pandemic, various hospitals have imposed mandatory hand washing to everyone prior entering the facilities, and when leaving. This study aimed to assess the hand washing compliance among visitors of a university referral hospital. Methods: A non-participatory observational study was conducted in the main entrance of the hospital from April 27 to May 3, 2020, to measure hand washing compliance of its visitors. The quality of hand washing was assessed via direct observation for compliance with the recommended World Health Organization (WHO) core steps. Data were collected using Open Data Kit (ODK) mobile application. Results: A total of 1,282 hospital visitors were observed, of which 874(68.2%) were males. Full hand washing compliances were observed among 0.9% (95% CI: 0.4-1.4) of the visitors. Withal, there was no difference in the compliances between genders (0.9% vs 0.7%, P = 0.745). Conclusion: Despite the fact that proper hand washing with soap and water is proven to be one of the effective ways in preventing the spread of COVID-19, a significant number of hospital visitors did not practice standard hand washing procedures. Improvements in this measure are urgently needed in the face of the current COVID-19 pandemic.


title: SARS-CoV-2 reactive T cells in uninfected individuals are likely expanded by beta-coronaviruses

text: The current pandemic is caused by the SARS-CoV-2 virus and large progress in understanding the pathology of the virus has been made since its emergence in late 2019. Several reports indicate short lasting immunity against endemic coronaviruses, which contrasts repeated reports that biobanked venous blood contains SARS-CoV-2 reactive T cells even before the outbreak in Wuhan. This suggests there exists a preformed T cell memory in individuals not exposed to the pandemic virus. Given the similarity of SARS-CoV-2 to other members of the Coronaviridae family, the endemic coronaviruses appear likely candidates to generate this T cell memory. However, given the apparent poor immunological memory created by the endemic coronaviruses, other immunity against other common pathogens might offer an alternative explanation. Here, we utilize a combination of epitope prediction and similarity to common human pathogens to identify potential sources of the SARS-CoV-2 T cell memory. We find that no common human virus, other than beta-coronaviruses, can explain the pre-existing SARS-CoV-2 reactive T cells in uninfected individuals. Our study suggests OC43 and HKU1 are the most likely pathogens giving rise to SARS-CoV-2 preformed immunity.


title: High-Dose Intravenous Immunoglobulin as a Therapeutic Option for Deteriorating Patients With Coronavirus Disease 2019

text: The outbreak of coronavirus disease 2019 (COVID-19) has spread rapidly in China. Until now, no definite effective treatment has been identified. We reported on 3 patients with severe COVID-19 who received high-dose intravenous immunoglobulin (IVIg) with satisfactory recovery. Based on these observations, randomized studies of high-dose IVIg should be considered in deteriorating patients infected with COVID-19.


title: Mechanistic understanding enables the rational design of salicylanilide combination therapies for Gram-negative infections

text: One avenue to combat multidrug-resistant Gram-negative bacteria is the co-administration of multiple drugs (combination therapy), which can be particularly promising if drugs synergize. The identification of synergistic drug combinations, however, is challenging. Detailed understanding of antibiotic mechanisms can address this issue by facilitating the rational design of improved combination therapies. Here, using diverse biochemical and genetic assays, we reveal the molecular mechanisms of niclosamide, a clinically-approved salicylanilide compound, and demonstrate its potential for Gram-negative combination therapies. We discovered that Gram-negative bacteria possess two innate resistance mechanisms that reduce their niclosamide susceptibility: a primary mechanism mediated by multidrug efflux pumps and a secondary mechanism of nitroreduction. When efflux was compromised, niclosamide became a potent antibiotic, dissipating the proton motive force (PMF), increasing oxidative stress and reducing ATP production to cause cell death. These insights guided the identification of diverse compounds that synergized with salicylanilides when co-administered (efflux inhibitors, membrane permeabilizers, and antibiotics that are expelled by PMF-dependent efflux), thus suggesting that salicylanilide compounds may have broad utility in combination therapies. We validate these findings in vivo using a murine abscess model, where we show that niclosamide synergizes with the membrane permeabilizing antibiotic colistin against high-density infections of multidrug-resistant Gram-negative clinical isolates. We further demonstrate that enhanced nitroreductase activity is a potential route to adaptive niclosamide resistance but show that this causes collateral susceptibility to clinical nitro-prodrug antibiotics. Thus, we highlight how mechanistic understanding of mode of action, innate/adaptive resistance, and synergy can rationally guide the discovery, development and stewardship of novel combination therapies. Importance There is a critical need for more effective treatments to combat multidrug-resistant Gram-negative infections. Combination therapies are a promising strategy, especially when these enable existing clinical drugs to be repurposed as antibiotics. We reveal the mechanisms of action and basis of innate Gram-negative resistance for the anthelmintic drug niclosamide, and subsequently exploit this information to demonstrate that niclosamide and analogs kill Gram-negative bacteria when combined with antibiotics that inhibit drug efflux or permeabilize membranes. We confirm the synergistic potential of niclosamide in vitro against a diverse range of recalcitrant Gram-negative clinical isolates, and in vivo in a mouse abscess model. We also demonstrate that nitroreductases can confer resistance to niclosamide, but show that evolution of these enzymes for enhanced niclosamide resistance confers a collateral sensitivity to other clinical antibiotics. Our results highlight how detailed mechanistic understanding can accelerate the evaluation and implementation of new combination therapies.


title: Monitoring Italian COVID-19 spread by an adaptive SEIRD model

text: Due to the recent diffusion of COVID-19 outbreak, the scientific community is making efforts in analysing models for understanding the present situation and predicting future scenarios. In this paper, we propose a Susceptible-Infected-Exposed-Recovered-Dead (SEIRD) differential model [Weitz J. S. and Dushoff J., Scientific reports, 2015] for the analysis and forecast of the COVID-19 spread in Italian regions, using the data from the Italian Protezione Civile from February 24th 2020. In this study, we investigate an adaptation of SEIRD that takes into account the actual policies of the Italian government, consisting of modelling the infection rate as a time-dependent function (SEIRD(rm)). Preliminary results on Lombardia and Emilia-Romagna regions confirm that SEIRD(rm) fits the data more accurately than the original SEIRD model with constant rate infection parameter. Moreover, the increased flexibility in the choice of the infection rate function makes it possible to better control the predictions due to the lockdown policy.


title: Association of the Covid-19 lockdown with smoking, drinking, and attempts to quit in England: an analysis of 2019-2020 data

text: Aim: To examine changes in smoking, drinking, and quitting/reduction behaviour following the Covid-19 lockdown in England. Design/setting: Monthly cross-sectional surveys representative of the adult population in England, aggregated before (April 2019 through February 2020) versus after (April 2020) the lockdown. Participants: 20,558 adults ([≥]16y). Measurements: The independent variable was the timing of the Covid-19 lockdown in England (before vs. after March 2020). Dependent variables were: prevalence of smoking and high-risk drinking; past-year cessation and quit attempts (among past-year smokers); past-year attempts to reduce alcohol consumption (among high-risk drinkers); and use of evidence-based (e.g., prescription medication/face-to-face behavioural support) and remote support (telephone support/websites/apps) for smoking cessation and alcohol reduction (among smokers/high-risk drinkers who made a quit/reduction attempt). Covariates included age, sex, social grade, region, and level of nicotine and alcohol dependence (as relevant). Findings: The Covid-19 lockdown was not associated with a significant change in smoking prevalence (17.0% (after) vs. 15.9% (before), OR=1.09[95%CI 0.95-1.24]), but was associated with increases in the rate of quit attempts (39.6% vs. 29.1%, ORadj=1.56[1.23-1.98]) and cessation (8.8% vs. 4.1%, ORadj=2.63[1.69-4.09]) among past-year smokers. Among smokers who tried to quit, there was no significant change in use of evidence-based support (50.0% vs. 51.5%, ORadj=1.10[0.72-1.68]) but use of remote support increased (10.9% vs. 2.7%, ORadj=3.59[1.56-8.23]). Lockdown was associated with increases in the prevalence of high-risk drinking (38.3% vs. 25.1%, OR=1.85[1.67-2.06]) but also alcohol reduction attempts by high-risk drinkers (28.5% vs. 15.3%, ORadj=2.16[1.77-2.64]). Among high-risk drinkers who made a reduction attempt, use of evidence-based support decreased (1.2% vs. 4.0%, ORadj=0.23[0.05-0.97]) and there was no significant change in use of remote support (6.9% vs. 6.1%, ORadj=1.32[0.64-2.75]). Conclusions: In England, prevalence of high-risk drinking but not smoking has increased since the Covid-19 lockdown. Smokers and high-risk drinkers are more likely than before lockdown to report trying to quit smoking or reduce their alcohol consumption, and rates of smoking cessation are higher. Smokers are no less likely than before lockdown to use cessation support, with increased uptake of remote support. However, use of evidence-based support for alcohol reduction by high-risk drinkers has decreased, with no compensatory increase in use of remote support.


L’activité physique en période de pandémie Covid-19


title: Scottish mental health and capacity law: The normal, pandemic and ‘new normal’

text: Abstract A state's real commitment to its international human rights obligations is never more challenged than when it faces emergency situations. Addressing actual and potential resourcing pressures arising from the COVID-19 pandemic has resulted in, amongst other things, modifications to Scottish mental health and capacity law and the issuing of new guidance relating to associated practice. Whether these emergency or ordinary measures are invoked during the crisis there are potential implications for the rights of persons with mental illness, learning disability and dementia notably those relating to individual autonomy and dignity. This article will consider areas of particular concern but how strict adherence to the legal, ethical and human rights framework in Scotland will help to reduce the risk of adverse consequences.


title: Creative and cultural work without filters: Covid-19 and exposed precarity in the creative economy

text: The precarious nature of creative and cultural work is widely acknowledged in academic literature. However, it has often been invisible in the eyes of policy and policymaking. As soon as the spread of Covid-19 started impacting local and national economies across the globe, many industry and policy bodies rushed into researching the impact of Covid-19 on the creative and cultural industries (CCIs) and the workers in the sector. The paper offers an insight into the key concerns of these organizations through the meta-analysis of the survey and research projects that are currently being undertaken in the context of the UK. The results highlight common concerns in relation to visible and invisible issues that need addressing in the sector. The paper concludes by questioning if Covid-19 represents a moment of crisis for the sector or has simply exposed the unsustainable price of creative and cultural work.


title: The Infection Rate of the Coronavirus Disease 2019 (COVID-19) in Wuhan, China

text: For the pandemic of COVID-19, the initial number of infections in Wuhan China has never been known or estimated properly. This data is critical to understand the current pandemic across the world, as well as to eliminate panic from overestimated fatality rate that has biased the public health policies of many countries. By our unique estimation with the data of a number of foreign government evacuations with thorough follow-up and etiological tests, it is safe to say that a large number of infections in Wuhan, China have not been diagnosed (the number of undiagnosed is much more than the final diagnosed number 50,333 to date).


title: Fibrinolytic niche is requested for alveolar type 2 cell-mediated alveologenesis and injury repair

text: COVID-19, SARS, and MERS are featured by fibrinolytic dysfunction. To test the role of the fibrinolytic niche in the regeneration of alveolar epithelium, we compared the self-renewing capacity of alveolar epithelial type 2 (AT2) cells and its differentiation to AT1 cells between wild type (wt) and fibrinolytic niche deficient mice (Plau−/− and Serpine1Tg). A significant reduction in both proliferation and differentiation of deficient AT2 cells was observed in vivo and in 3D organoid cultures. This decrease was mainly restored by uPA derived A6 peptide, a binding fragment to CD44 receptors. The proliferative and differential rate of CD44+ AT2 cells was greater than that of CD44− controls. There was a reduction in transepithelial ion transport in deficient monolayers compared to wt cells. Moreover, we found a marked suppression in total AT2 cells and CD44+ subpopulation in lungs from brain dead patients with acute respiratory distress syndrome (ARDS) and a mouse model infected by influenza viruses. Thus, we demonstrate that the fibrinolytic niche can regulate AT2-mediated homeostasis and regeneration via a novel uPA-A6-CD44+-ENaC cascade.


title: SARS-CoV-2 transmission in cancer patients of a tertiary hospital in Wuhan

text: In December 2019, an outbreak of atypical pneumonia known as 2019 novel coronavirus disease (COVID-19) occurred in Wuhan, China. This new type of pneumonia is characterized by rapid human-to-human transmission. Among the different disease types, cancer patients are often recalled to the hospital for treatment and disease surveillance, and the majority of cancer treatments such as chemotherapy and radiotherapy are immunosuppressive. This prompts us to consider if cancer patients were at an elevated risk of SARS-CoV-2 infection. A total of 1,524 cancer patients who were managed at our tertiary cancer institution-Zhongnan hospital of Wuhan University were reviewed during the period of Dec 30, 2019 to Feb 17, 2020. It was found that cancer patients had an estimated 2-fold increased risk of COVID-19 than the general population. We identified twelve patients who were infected with SARS-CoV-2, with two recorded deaths (16.7%), albeit one patient passed away from a COVID-19 unrelated cause. Interestingly, only five of these patients were ongoing treatment at the time of contracting the virus, suggesting that hospital visitation was the likely factor contributing to the elevated incidence in cancer patients. Moreover, we also observed that the incidence of severe COVID-19 was not higher than in the general population. Consequently, for cancer patients who require treatment, proper isolation protocols must be in place to mitigate the risk of SARS-CoV-2 infection.


title: High risk of infection caused posttraumatic stress symptoms in individuals with poor sleep quality: A study on influence of coronavirus disease (COVID-19) in China

text: The influence of the outbreak of coronavirus disease (COVID-19) on mental health was poorly understood. The present study aimed to exam sleep problems and posttraumatic stress symptoms (PTSS) in Chinese immediately after the massive outbreak of COVID-19. A total of 2027 Chinese participated in the present study. Wuhan-expose history, sleep quality and PTSS were measured with self-rating scales. Results showed that there were significant differences of PCL-5 and of sleep quality scores in different data-collection dates (ps<0.05). There were significant differences of PCL-5 scores (p<0.05) and latency onset of sleep (p<0.05) between participants with and without Wuhan-expose history. The interaction effect of Wuhan exposure history × sleep quality significantly influenced PCL-5 (ps<0.05). These results indicate that keeping good sleep quality in individuals with high infectious risk is a way to prevent PTSS.


COVID-19 in homeless populations: unique challenges and opportunities


title: COVID-19 length of hospital stay: a systematic review and data synthesis

text: Background The COVID-19 pandemic has placed an unprecedented strain on health systems, with rapidly increasing demand for healthcare in hospitals and intensive care units (ICUs) worldwide. As the pandemic escalates, determining the resulting needs for healthcare resources (beds, staff, equipment) has become a key priority for many countries. Projecting future demand requires estimates of how long patients with COVID-19 need different levels of hospital care. Methods We performed a systematic review to gather data on length of stay (LoS) of patients with COVID-19 in hospital and in ICU. We subsequently developed a method to generate LoS distributions which combines summary statistics reported in multiple studies, accounting for differences in sample sizes. Applying this approach we provide distributions for general hospital and ICU LoS from studies in China and elsewhere, for use by the community. Results We identified 52 studies, the majority from China (46/52). Median hospital LoS ranged from 4 to 53 days within China, and 4 to 21 days outside of China, across 45 studies. ICU LoS was reported by eight studies - four each within and outside China - with median values ranging from 6 to 12 and 4 to 19 days, respectively. Our summary distributions have a median hospital LoS of 14 (IQR: 10-19) days for China, compared with 5 (IQR: 3-9) days outside of China. For ICU, the summary distributions are more similar (median (IQR) of 8 (5-13) days for China and 7 (4-11) days outside of China). There was a visible difference by discharge status, with patients who were discharged alive having longer LoS than those who died during their admission, but no trend associated with study date. Conclusion Patients with COVID-19 in China appeared to remain in hospital for longer than elsewhere. This may be explained by differences in criteria for admission and discharge between countries, and different timing within the pandemic. In the absence of local data, the combined summary LoS distributions provided here can be used to model bed demands for contingency planning and then updated, with the novel method presented here, as more studies with aggregated statistics emerge outside China.


title: A Strategy to Treat COVID-19 Disease with Targeted Delivery of Inhalable Liposomal Hydroxychloroquine: A Non-clinical Pharmacokinetic Study

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly identified pathogen causing coronavirus disease 2019 (COVID-19) pandemic. Hydroxychloroquine (HCQ), an antimalarial and anti-inflammatory drug, has been shown to inhibit SARS-CoV-2 infection in vitro and tested in clinical studies. However, lung concentration (6.7 µg/mL) to predict the in vivo antiviral efficacy might not be achievable with the currently proposed oral dosing regimen. Further, a high cumulative doses of HCQ may raise concerns of systemic toxicity, including cardiotoxicity. Here, we described a non-clinical study to investigate the pharmacokinetics of a novel formulation of liposomal HCQ administrated by intratracheal (IT) instillation in Sprague-Dawley (SD) rats which achieved 129.4 µg/g (Cmax) in the lung. Compared to unformulated HCQ administered intravenous (IV), liposomal HCQ with normalized dose showed higher (∼30-fold) lung exposure, longer (∼2.5-fold) half-life in lung, but lower blood exposure with ∼20% of Cmax and 74% of AUC and lower heart exposure with 24% of Cmax and 58% of AUC. In conclusion, the pharmacokinetics results in an animal model demonstrate the proof of concept that inhalable liposomal HCQ may provide clinical benefit and serve as a potential treatment for COVID-19.


title: SARS-CoV-2 detection with CRISPR diagnostics

text: The novel coronavirus (CoV) disease termed COVID-19 (Coronavirus Disease-19) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) is causing a massive pandemic worldwide, threatening public health systems across the globe. During this ongoing COVID-19 outbreak, nucleic acid detection has played an important role in early diagnosis. Here we report a SARS-CoV-2 detection protocol using a CRISPR-based CRISPR diagnostic platform - CDetection (Cas12b-mediated DNA detection). By combining sample treatment protocols and nucleic acid amplification methods with CDetection, we have established an integrated viral nucleic acid detection platform - CASdetec (CRISPR-assisted detection). The detection limit of CASdetec for SARS-CoV-2 pseudovirus is 1 × 104 copies/mL, with no cross reactivity observed. Our assay design and optimization process can provide guidance for future CRISPR-based nucleic acid detection assay development and optimization.


title: Construction of Epitope-Based Peptide Vaccine Against SARS-CoV-2: Immunoinformatics Study

text: Recently, a novel coronavirus (SARS-CoV-2) appeared which is conscientious for the current outbreak in China and rapidly spread worldwide Unluckily, there is no approved vaccine found against SARS-CoV-2 Therefore, there is an urgent need for designing a suitable peptide vaccine constituent against the SARS-CoV-2 In this study, we characterized the spike glycoprotein of SARS-CoV-2 to obtain immunogenic epitopes In addition, we used 58 SARS-CoV-2 isolates were retrieved from the Global Initiative on Sharing All Influenza Data (GISAID) and National Center for Biotechnology Information (NCBI), then aligned to obtain the conserved region of SARS-CoV-2 spike glycoprotein The interaction between the conserved region with ACE2 receptor, a SARS-CoV-2 receptor on the host cell, has been evaluated through molecular docking approach The B-cell epitope was identified using the immune epitope database (IEDB) web server Interestingly, we recommend Pep_4 ADHQPQTFVNTELH as a epitope-based peptide vaccine candidate to deal with the SARS-CoV-2 outbreak Pep_4 has a high level of immunogenicity and does not trigger autoimmune mechanisms Pep_4 is capable of forming BCR/Fab molecular complexes with the lowest binding energy for activation of transduction signal the direct B-cell immune response However, further study is suggested for confirmation (in vitro and in vivo)


Descriptive characteristics of hospitalized adult smokers and never-smokers with COVID-19


title: Therapeutic effectiveness of interferon-alpha2b against COVID-19: the Cuban experience

text: Background Effective therapies are needed to control the SARS-Cov-2 infection pandemic and reduce mortality associated with COVID-19. Several clinical studies have provided evidence for the antiviral effects of type I interferons (IFNs) in patients with respiratory coronaviruses. This study assessed the therapeutic efficacy of IFN-alpha 2b in patients infected with SARS-CoV-2 during the first month after the outbreak began in Cuba. Method This multicenter prospective observational study was conducted in 16 hospitals in 8 Cuban provinces. Participants were patients with confirmed SARS-CoV-2 infection detected from throat swab specimens by real time RT-PCR who gave informed consent and had no contraindications for IFN treatment. Patients received therapy as per the Cuban COVID protocol, that included a combination of oral antivirals (lopinavir/ritonavir and chloroquine) with intramuscular administration of IFN-alpha 2b (Heberon Alpha R, Center for Genetic Engineering and Biotechnology, Havana), 3 times per week, for 2 weeks. The primary endpoint was the proportion of patients discharged from hospital (without clinical and radiological symptoms and non-detectable virus by RT-PCR). The secondary endpoint was the case fatality rate (CFR), defined as the number of confirmed deaths divided by the number of confirmed cases. Results From March 11th to April 14th, 814 patients were confirmed SARS-CoV-2 positive in Cuba, 761 (93.4%) were treated with Heberon Alpha R and 53 received the approved protocol without IFN treatment. The proportion of fully recovered patients was higher in the IFN-treated compared with non-IFN treated group (95.4% vs 26.1%, p<0.01). The CFR for all patients was 2.95%, and for those patients who received IFN-alpha 2b the CFR was reduce to 0.92. The estimated global CFR is 6.34% and 4.05% for the Americas reported by WHO and PAHO, respectively. In this study, 82 patients (10.1%) required intensive care and, of these, 42 (5.5%) were treated with IFN. Conclusions This report provides preliminary evidence for the therapeutic effectiveness of IFN alpha-2b for COVID-19 and suggests that the use of Heberon Alpha R may contribute to complete recovery.


Covid-19: Surviving the long road ahead


title: Medical treatment of 55 patients with COVID-19 from seven cities in northeast China who fully recovered: a single-center, retrospective, observational study

text: Background: COVID-19 is an emerging disease caused by the SARS-CoV-2 virus; no specific medication has been identified to date. We aimed to investigate the administered medications and intervention times for patients who completely recovered from COVID-19. Methods: This single-center, retrospective, and observational study included 55 patients with COVID-19 who were transferred to Shenyang Sixth People's Hospital between January 20 and March 15, 2020. Demographic information, symptoms, laboratory indicators, treatment processes, and clinical outcomes were collected. Administered drugs and intervention times were compared in 47 and eight patients with mild and severe symptoms, respectively. Findings: All 55 patients recovered. Fifty-three patients (96.36%) received antiviral therapy, including 45 in the mild group (median treatment: 14 days; 17 received umifenovir) and all eight severe-group patients (median treatment: 17.5 days; four received lopinavir/ritonavir). Twenty-nine patients (52.72%) were administered antibiotics, including 21 in the mild group (median treatment: 13.5 days; 15 received moxifloxacin) and all eight in the severe group (median treatment: 9 days; two received linezolid). Moreover, seven patients (12.72%) were treated with glucocorticoids and nine (16.36%) with immunomodulators. Interpretation: Given the 100% recovery rate, early administration of antiviral drugs can be considered. Umifenovir may benefit patients with mild symptoms, while lopinavir/ritonavir may benefit those with severe symptoms. Prophylactic administration of common antibiotics may reduce the risk of co-infection. The use of glucocorticoids is usually not necessary.


title: COVID-19 apparent reproductive number dropped during Spain's nationwide dropdown, then spiked at lower-incidence regions

text: COVID-19 pandemic has rapidly spread worldwide. Spain has suffered one of the largest nationwide bursts, particularly in the highly populated areas of Madrid and Barcelona (two of the five largest conurbations in Europe). We used segmented regression analyses to identify shifts in the evolution of the apparent reproductive number (Rt) reported for 16 Spanish administrative regions. We associate these breaking points with a timeline of key containment measures taken by national and regional governments, applying time lags for the time from contagion to case detection, with their associated errors. Results show an early decrease of Rt that preceded the nationwide lockdown; a generalized, sharp decrease in Rt associated with such lockdown; a low impact of the strengthened lockdown, with a flattening of Rt evolution in high-incidence regions regions - but increases in Rt at low-incidence regions; and an increase in Rt, associated to the relaxation of the lockdown measures, in ten regions. These results evidence the importance of generalized lockdown measures to contain COVID-19 spread; and the limited effect of the subsequent application of a stricter lockdown (restrictions to all non-essential economic activities). Most importantly, they highlight the importance of maintaining strong social distancing measures and strengthening public health control during lockdown de-escalation.


title: Coronavirus disease-19: Summary of 2,370 Contact Investigations of the First 30 Cases in the Republic of Korea

text: Between January 24 and March 10, of a total of 2,370 individuals who had contacted the first 30 cases of COVID19, 13 were found to have COVID19, resulting secondary attack rate of 0.55% (95% CI 0.31 to 0.96). Of 119 household contacts, 9 had infections resulting secondary attack rate of 7.56 (95% CI 3.73 to 14.26).


title: Associations with covid-19 hospitalisation amongst 406,793 adults: the UK Biobank prospective cohort study

text: OBJECTIVES: To identify the sociodemographic, lifestyle, comorbidity and antihypertensive medication associations with the development of hospitalisation with covid-19 in an English population. DESIGN: Prospective cohort study SETTING: The population-based UK Biobank study was linked to English covid-19 test results. PARTICIPANTS: Individuals resident in England and alive in 2020. MAIN OUTCOME MEASURES: Cases (n=605) were defined by a positive covid-19 test result conducted between 16th March and 16th April 2020, during a restricted testing policy for hospitalised individuals with severe disease. RESULTS: A total of 406,793 participants were included. Mean age on 1st January 2020 was 68 years (range 48 to 85 years). 55% were women. In multivariable models, major independent risk factors for hospitalisation with covid-19 were male sex (odds ratio 1.52; 95% confidence interval 1.28 to 1.81; P<0.001), South Asian ethnicity (2.02; 1.28 to 3.17; P=0.002) or black ethnicity (3.09; 2.18 to 4.38; P<0.001) compared to white ethnicity, greater residential deprivation (1.92 for most deprived quartile compared to least deprived quartile; 1.50 to 2.47; P<0.001), higher BMI (2.04 for BMI >35 compared to <25 Kg/m2; 1.50 to 2.77; P<0.001), former smoking (1.39 compared to never smoked; 1.16 to 1.66; P<0.001), and comorbidities hypertension (1.28; 1.06 to 1.53; P=0.009) and chronic obstructive pulmonary disease (1.81; 1.34 to 2.44; P<0.001). Increased risk was observed with increasing number of antihypertensive medications used rather than any individual class. CONCLUSION: Understanding why these factors confer increased risk of severe covid-19 in the population may help elucidate the underlying mechanisms as well as inform strategy and policy to prevent this disease and its consequences. We found no evidence of increased risk with specific classes of antihypertensive medication.


title: COVID-19 Outbreak Situations in Bangladesh: An Empirical Analysis

text: COVID-19 disease, as popularly known as Coronavirus 2019 disease, has been emerged from Wuhan, China in December 2019 and now is a pandemic for almost every nation in the earth. It affects every country without considering country's race, nationality and economic status. This paper aims at analysing primarily the current situations of Bangladesh and predicting infections and deaths for moderated term intervals by a proposed projection technique called Infection Trajectory-Pathway Strategy (ITPS) and for short term intervals prediction for total infections, deaths along with total number of severe patients and Intensive Care Unit (ICU) patients by polynomial regression modeling approach. Since April 7, Bangladesh has started to face critical situations as the number of infections has accelerated very fast in the following days. However, the fatality rate decreases considerably from 15.7 on April 1 to 4.9 on April 14, which is still high among the south asian countries. Of the 1012 cases reported on April 14, almost 70\% are the male, 42\% are from the capital Dhaka. We have found that the potential pathway of infections for Bangldesh would be the similar pathways that are experienced by Austria, Netherlands, Israel, France and United Kingdom. These countries are ahead a number of weeks and days in terms of infection cases since their 100-th confirmed cases. Our proposed projection method ITPS suggests that by May 10, Bangladesh will cross 12000 incidences and 720 deaths which, by May 16 will be 27000 and 1644 respectively. On the other hand, the regression model suggests that by the end of April, total number of infections, deaths, severe patients and ICU patients will be 5780, 347, 775, and 694 respectively. This study will be favorable for the administrative units of Bangladesh to plan for the next few weeks and to consider various aspects related to the control of COVID-19 outspread in Bangladesh


The Muslim Call to Prayer in Canada's Pandemic Soundscape


Biotech Plays Critical Role in Protecting Against Coronavirus Outbreak


title: Impact of COVID-19 on 2020 US life expectancy for the Black and Latino populations

text: The Black and Latino populations have experienced a disproportionate burden of COVID-19 morbidity and mortality, reflecting persistent structural inequalities that increase risk of exposure to COVID-19 and risk of death for those infected. According to the National Center for Health Statistics, as of July 4, 2020, deaths to Black and Latino individuals comprised 23% and 17%, respectively, of the approximately 115,000 COVID-19 deaths. COVID-19 mortality is likely to result in a larger decline in life expectancy during 2020 than the US has experienced for decades as well as a particularly large reduction for Black and Latino individuals. We estimate life expectancy at birth and at age 65 for 2020, by race and ethnicity, using four scenarios of deaths-one in which the COVID-19 pandemic had not occurred and three including COVID-19 mortality projections produced by the Institute for Health Metrics and Evaluation. Our most likely estimate indicates a reduction in life expectancy at birth greater than 1.5 years for both the Black and Latino populations, which is one year larger than the reduction for whites. This would imply that the Black-white gap would increase by 30%, from 3.6 to 4.7 years, thereby eliminating progress made in reducing this differential since 2008 and reversing an overall trend of steeper mortality declines among the Black population since the early 1990s. Latinos, who have consistently experienced lower mortality than whites (a phenomenon known as the Latino or Hispanic paradox), would see their survival advantage decline by 36%, equivalent to its magnitude in 2006.


title: In-house modification and improvement of the CDC real-time PCR diagnostic assay for SARS-CoV-2 detection.

text: The world is currently facing an unprecedented pandemic caused by the novel coronavirus SARS-CoV-2 (COVID-19) which was first reported in late 2019 by China to the World Health Organization (WHO). The containment strategy for COVID-19, which has non-specific flu-like symptoms and where upwards of 80% of the affected has either mild or no symptoms, is critically centered upon diagnostic testing, tracking and isolation. Thus, the development of specific and sensitive diagnostic tests for COVID-19 is key towards the first successful step of disease management. Public health organizations like the WHO and the US-based Centers for Disease Control and Prevention (CDC) have developed real-time PCR (RT-PCR) based diagnostic tests to aid in the detection of acute infection. In this study we sought to modify the CDC RT-PCR diagnostic assay protocol to increase its sensitivity and to make the assay directly portable to health care providers in a community-based hospital setting. A number of modifications to the original protocol were tested. Increasing the RT-PCR annealing temperature by 7{degrees}C to 62{degrees}C was associated with the most significant improvement in sensitivity, wherein the cycle-threshold (Ct) value for the N2 assay was reduced by ~3 units, in effect both reducing the overall number of inconclusive results and yielding N1/N2 assays to have similar Ct values. The limit of detection of the modified assay was also improved (0.86 RNA copies/l for both nCoV 2019_N1/N2 assays) compared to the CDC RT-PCR diagnostic assay (1 and 3.16 RNA copies/l for nCoV 2019_N1 and N2 assay, respectively). Using this modification, there was no significant effect on SARS-CoV-2 detection rate when viral RNA extraction was performed either manually or through an automated extraction method. We believe this modified protocol allows for more sensitive detection of the virus which in turn will be useful for pandemic management.


title: Bioinformatics Study on Structural Proteins of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) For Better Understanding the Vaccine Development

text: Novel coronavirus 2019 (2019-nCoV), also known as SARS-CoV-2), leads high morbidity and mortality in global epidemics. Four structural proteins (surface glycoprotein (QIQ22760.1), envelop glycoprotein (QIQ22762.1), nucleocapsid phosphoprotein (QIQ22768.1) and membrane glycoprotein (QIQ22763.1)) of SARS-CoV-2 are extracted from the NCBI database and further analyzed with ExPASy ProtParam tool. Lucien is the highest in envelope, surface and membrane glycoprotein that is an optimal environment for rapid virus fixation on host cell's surface to the receptor molecule. Transmembrane region prediction was performed by SOSUI server. For all structural proteins, except nucleocapsid Phosphoprotein, the trans-membrane prediction indicates that the virus can enter the host easily. Domain analysis was done by SMART tool. Domain information helps in the function of the viral protein. Lastly, the 3D structure prediction was carried out by Swiss Model and the result validation was achieved by PROCHECK. Such models are the starting point of the community for structural drug and vaccine designs as well as virtual computational screening.


title: Coronavirus disruptions could hurt North Korea’s efforts to treat tuberculosis

text: North Korea watchers warn that the country’s aggressive measures to defend itself against COVID-19, the illness caused by the novel coronavirus, are hobbling efforts to combat tuberculosis (TB) and other infectious diseases Sandwiched between two COVID-19 hot spots—China and South Korea—North Korea at the end of January suspended international flights and severed its rail link with China Since then, cargo containers headed to North Korea’s port in Nampo have stalled in Dalian, China, snagged on red tape in China and new quarantine procedures in Nampo The only way in and out of North Korea now is a road crossing on its northern border with China North Korea’s state media has said the border restrictions will remain in effect until COVID-19 has stopped spreading or a vaccine is available That puts North Korea’s thousands of TB patients in a precarious situation Three containers with first-line TB drugs are among hundreds held up in Dalian, says a U S -based humanitarian organization official, who requested anonymity The official notes that North Korea’s supply of first-line TB drugs is expected to run out in May or June The situation is even more perilous for North Koreans infected with multidrug-resistant TB strains Treatment lapses can lead to even more recalcitrant strains “Truly it opens grave concern” about the development of extensively drug-resistant TB in North Korea, the official says Related


title: Predictive performance of international COVID-19 mortality forecasting models

text: Forecasting models have provided timely and critical information about the course of the COVID-19 pandemic, predicting both the timing of peak mortality, and the total magnitude of mortality, which can guide health system response and resource allocation. Out-of-sample predictive validation--checking how well past versions of forecasting models predict subsequently observed trends--provides insight into future model performance. As data and models are updated regularly, a publicly available, transparent, and reproducible framework is needed to evaluate them in an ongoing manner. We reviewed 384 published and unpublished COVID-19 forecasting models, and evaluated seven models for which publicly available, multi-country, and date-versioned mortality estimates could be downloaded. These included those modeled by: DELPHI-MIT (Delphi), Youyang Gu (YYG), the Los Alamos National Laboratory (LANL), Imperial College London (Imperial), and three models produced by the Institute for Health Metrics and Evaluation (IHME), a curve fit model (IHME-CF), a hybrid curve fit and epidemiological compartment model (IHME-CF SEIR), and a hybrid mortality spline and epidemiological compartment model (IHME - MS SEIR). Collectively models covered 171 countries, as well as the 50 states of the United States, and Washington, D.C., and accounted for >99% of all reported COVID-19 deaths on July 11th, 2020. As expected, errors in mortality predictions increased with a larger number of weeks of extrapolation. For the most recent models, released in June, at four weeks of forecasting the best performing model was the IHME-MS SEIR model, with a cumulative median absolute percent error of 6.4%, followed by YYG (6.5%) and LANL (8.0%). Looking across models, errors in cumulative mortality predictions were highest in sub-Saharan Africa and lowest in high-income countries, reflecting differences in data availability and prediction difficulty in earlier vs. later stages of the epidemic. For peak timing prediction, among models released in April, median absolute error values at six weeks ranged from 23 days for the IHME-CF model to 36 days for the YYG model. In sum, we provide a publicly available dataset and evaluation framework for assessing the predictive validity of COVID-19 mortality forecasts. We find substantial variation in predictive performance between models, and note large differences in average predictive validity between regions, highlighting priority areas for further study in sub-Saharan Africa and other emerging-epidemic contexts.