title: A direct RT-qPCR approach to test large numbers of individuals for SARS-CoV-2

text: SARS-CoV-2 causes substantial morbidity and mortality in elderly and immunocompromised individuals, particularly in retirement homes, where transmission from asymptomatic staff and visitors may introduce the infection. Here we present a cheap and fast approach to detect SARS-CoV-2 in single or pooled gargle lavages ('mouthwashes'). With this approach, we test all staff at a nursing home daily over a period of three weeks in order to reduce the risk that the infection penetrates the facility. This or similar approaches could be implemented to protect hospitals, nursing homes and other institutions in this and future viral epidemics.


title: Sensitivity Optimisation of Tuberculosis Bioaerosol Sampling

text: Introduction: Detection of Mycobacterium tuberculosis (Mtb) in patient-derived bioaerosol is a potential tool to measure source case infectiousness. However, current bioaerosol sampling approaches have reported low detection yields in sputum-positive TB cases. To increase the utility of bioaerosol sampling, we present advances in bioaerosol collection and Mtb identification that improve detection yields. Methods: A previously described Respiratory Aerosol Sampling Chamber (RASC) protocol, or 'RASC-1', was modified to incorporate liquid collection of bioaerosol using a high-flow wet-walled cyclone (RASC-2). Individuals with GeneXpert-positive pulmonary TB were sampled pre-treatment over 60-minutes. Putative Mtb bacilli were detected in collected fluid by fluorescence microscopy utilising DMN-Trehalose. Exhaled air and bioaerosol volumes were estimated using continuous CO2 monitoring and airborne particle counting, respectively. Mtb capture was calculated per exhaled air volume sampled and bioaerosol volume for RASC-1 (n=35) and for RASC-2 (n=21). Empty chamber samples were collected between patients as controls. Results: The optimised RASC-2 protocol sampled a median of 258.4L (IQR: 226.9-273.6) of exhaled air per patient compared with 27.5L (IQR: 23.6-30.3) for RASC-1 (p<0.0001). Bioaerosol volume collection was estimated at 2.3nL (IQR: 1.1-3.6) for RASC-2 compared with 0.08nL (IQR: 0.05-0.10) for RASC-1 (p<0.0001). The detection yield of viable Mtb improved from 43% (median 2 CFU, range: 1-14) to 95% (median 20.5 DMN-Trehalose positive bacilli, range: 2-155). These improvements represent a lowering of the limit of detection in the RASC-2 platform to 0.9 Mtb bacilli per 100L of exhaled air from 3.3 Mtb bacilli per 100L (RASC-1). Conclusion: This study demonstrates that technical improvements in particle collection together with sensitive detection enable rapid quantitation of viable Mtb in bioaerosols of sputum positive TB cases. Increased sampling sensitivity may allow future TB transmission studies to be extended to sputum-negative and subclinical individuals, and suggests the potential utility of bioaerosol measurement for rapid intervention in other airborne infectious diseases.


title: Array-based analysis of SARS-CoV-2, other coronaviruses, and influenza antibodies in convalescent COVID-19 patients

text: Detection of antibodies to upper respiratory pathogens is critical to surveillance, assessment of the immune status of individuals, vaccine development, and basic biology. The urgent need for antibody detection tools has proven particularly acute in the COVID-19 era. We report a multiplex label-free antigen microarray on the Arrayed Imaging Reflectometry (AIR) platform for detection of antibodies to SARS-CoV-2, SARS-CoV-1, MERS, three circulating coronavirus strains (HKU1, 229E, OC43) and three strains of influenza. We find that the array is readily able to distinguish uninfected from convalescent COVID-19 subjects, and provides quantitative information about total Ig, as well as IgG- and IgM-specific responses.


Rashford, racism, and bankrupt excuses


title: Impact of COVID-19 related lockdown on cognition and emotion: A pilot study

text: COVID-19 pandemic has posed an unprecedented challenge in front of the world contributed mostly by social distancing and lockdown. Among several other effects this pandemic has wreaked havoc on the psychology and cognition of people across the globe. In this paper we attempted to find out the impact of lockdown and social isolation on the cognition and emotion of young healthy adults with high education (n=43) by means of a questionnaire sent through email. We found that more than 50% of the participants had some kind of emotional or cognitive (dysexecutive) symptoms, as calculated through emotional symptom index (ESI) and cognitive symptom index (CSI). The correlation between cognitive and emotional symptoms was also found to be moderately strong (0.59). Although it is a pilot study and larger samples are required to draw firm conclusion, the results argue in favor of a negative impact on the cognition and emotion of healthy educated young people caused by the COVID-19 related lockdown. It can be conjectured that, if taking an older sample with a lower education, emotional and cognitive changes would be more evident.


title: A Rapid Review of the Asymptomatic Proportion of PCR-Confirmed SARS-CoV-2 Infections in Community Settings

text: Background: Up to 80% of active SARS-CoV-2 infections are proposed to be asymptomatic based on cross-sectional studies. However, accurate estimates of the asymptomatic proportion require systematic detection and follow-up to differentiate between truly asymptomatic and pre-symptomatic cases. We conducted a rapid review and meta-analysis of current evidence regarding the asymptomatic proportion of PCR-confirmed SARS-CoV-2 infections based on methodologically-appropriate studies in community settings. Methods: We searched Medline and EMBASE for peer-reviewed articles, and BioRxiv and MedRxiv for pre-prints published prior to 05/05/2020. We included studies based in community settings that involved systematic PCR testing on participants and follow-up symptom monitoring regardless of symptom status. We extracted data on study characteristics, frequencies of PCR-confirmed infections by symptom status, and (if available) cycle threshold values and/or duration of viral shedding by symptom status. We computed estimates of the asymptomatic proportion and 95% confidence intervals for each study and overall using random effect meta-analysis. Findings: We screened 270 studies and included 6. The pooled estimate for the asymptomatic proportion of SARS-CoV-2 infections was 11% (95% CI 4%-18%). Estimates of baseline viral load appeared to be similar for asymptomatic and symptomatic cases based on available data in three studies, though detailed reporting of cycle threshold values and natural history of viral shedding by symptom status was limited. Interpretation: The asymptomatic proportion of SARS-CoV-2 infections is relatively low when estimated from methodologically-appropriate studies. Further investigation into the degree and duration of infectiousness for asymptomatic infections is warranted. Funding: Medical Research Council


title: Effectiveness of isolation, testing, contact tracing and physical distancing on reducing transmission of SARS-CoV-2 in different settings

text: Isolation of symptomatic cases and tracing of contacts has been used as an early COVID-19 containment measure in many countries, with additional physical distancing measures also introduced as outbreaks have grown. To maintain control of infection while also reducing disruption to populations, there is a need to understand what combination of measures - including novel digital tracing approaches and less intensive physical distancing - may be required to reduce transmission. Using a model of individual-level transmission stratified by setting (household, work, school, other) based on BBC Pandemic data from 40,162 UK participants, we simulated the impact of a range of different testing, isolation, tracing and physical distancing scenarios. As well as estimating reduction in effective reproduction number, we estimated, for a given level of COVID-19 incidence, the number of contacts that would be newly quarantined each day under different strategies. Under optimistic but plausible assumptions, we estimated that combined testing and tracing strategies would reduce transmission more than mass testing or self-isolation alone (50-65% compared to 2-30%). If limits are placed on gatherings outside of home/school/work (e.g. maximum of 4 daily contacts in other settings), then manual contact tracing of acquaintances only could have a similar effect on transmission reduction as detailed contact tracing. In a scenario where there were 10,000 new symptomatic cases per day, we estimated in most contact tracing strategies, 140,000 to 390,000 contacts would be newly quarantined each day. Consistent with previous modelling studies and country-specific COVID-19 responses to date, our analysis estimates that a high proportion of cases would need to self-isolate and a high proportion of their contacts to be successfully traced to ensure an effective reproduction number that is below one in the absence of other measures. If combined with moderate physical distancing measures, self-isolation and contact tracing would be more likely to achieve control.


Novel coronavirus (2019-nCoV) update: What we know and what is unknown


The experience of the COVID-19 pandemic in a UK learning disability service_ lost in a sea of ever changing variables–a perspective


title: COVID-19: Saving lives and livelihoods using population density driven testing

text: SARS-CoV-2 transmission risk generally increases with proximity of those shedding the virus to those susceptible to infection. Thus, this risk is a function of both number of people and the area which they occupy. However, the latter continues to evade COVID-19 testing policy. Increased testing in areas with lower population density, has the potential to induce a false sense of security even as cases continue to rise sharply overall.


title: &BETA;-sitosterol: Isolation from muntingia calabura linn. bark extract, structural elucidation, and molecular docking studies as potential inhibitor of sars-cov-2 mpro (COVID-19)

text: Objective: A novel human coronavirus, labeled as SARS-CoV-2 (COVID-19), causing pneumonia is spreading around the world. At present, there are no specific treatments for COVID-19. β-sitosterol is well known for its multiple biological actions. This research aims to isolate and study the binding affinity of β-sitosterol for SARS-CoV-2 (COVID-19) main protease (Mpro). Methods: Extraction and column chromatography was performed to isolate the β-sitosterol from an n-hexane extract of Muntingia calabura bark followed by thin-layer chromatography (TLC), high-performance TLC (HPTLC), Fourier-Transform infrared (FTIR), and ultraviolet-visible spectroscopy. The molecular docking studies were performed on SARS-CoV-2 Mpro to determine the binding affinity of the β-sitosterol using PyRx Virtual Screening Tool. Results: In the present study, preliminary phytochemical screening showed the presence of carbohydrate, steroid, terpenoid, and flavonoid compounds. A total of 115 fractions was collected from column chromatography using benzene as a solvent by an isocratic elution technique. HPTLC fingerprinting analysis showed the presence of β-sitosterol under 366 nm. FTIR characterization was performed of the same fraction which gives the absorption peaks which resembles the β-sitosterol structure. Conclusion: The overall study concludes this method can be considered as a standard method for isolation of β-sitosterol from M. calabura bark. Favipiravir has a less binding affinity, i.e. -5.7 kcal/mol than β-sitosterol which has -6.9 kcal/mol. The number of hydrogen bonds formed by the favipiravir is much more, i.e., 4 than β-sitosterol which formed only 01 hydrogen bonds with SARS-CoV-2 Mpro.


title: Investigating selection bias of online surveys on coronavirus-related behavioral outcomes

text: The coronavirus SARS-CoV-2 outbreak has stimulated numerous online surveys that are mainly based on online convenience samples or commercial online access panels where par-ticipants select themselves. The results are, nevertheless, often generalized to the general pop-ulation. In our paper we investigate the potential bias that is introduced by respondents’ self-selection. The analysis is based on survey data of the “GESIS Panel Special Survey on the Coronavirus SARS-CoV-2 Outbreak in Germany”, together with background information of the GESIS Panel. Our analyses show indication of a nonignorable amount of selection bias for measures of personality traits among online survey respondents. This provides some evidence that participating in an online survey and complying with measures that can minimize the risk of being infected with the SARS-CoV-2 virus are confounded. Hence, generalizing these results to the general population bears the risk of over-or underestimating the share of the population that complies with specific measures.


title: Validation of the Kuwait Progression Indicator Score for predicting progression of severity in COVID19

text: Introduction: Identifying patients with COVID19, at risk of having a severe clinical course during their hospitalization is important for appropriate allocation of clinical resources. We recently described the Kuwait Progression Indicator based on laboratory findings, in an initial training cohort derived from the first series of 1096 consecutive patients admitted to Jaber AlAhmad AlSabah Hospital in Kuwait. The aim of this study was to validate the KPI scoring system in an independent cohort of patients with COVID19. Methodology: Data was collected prospectively for consecutive patients admitted to Jaber AlAhmad AlSabah Hospital in Kuwait between 24th February till 28th April 2020. Patients were grouped according to the severity of their clinical course as their main outcome, based on clinical and radiological parameters, with ICU admission and death as secondary outcomes. Model discrimination was assessed through the area under the receiver operating characteristic curve (AUC) while model calibration was assessed through a calibration plot and measures of slope and calibration in the large (CITL). Results: Of 752 patients not used in model development previously, 414 met the criteria for inclusion in this validation study. The baseline characteristics for these 752 patients were similar to the patients that were included in our validation cohort. The area under the curve was equal to 0.904 (95% CI, between 0.867 to 0.942), indicating good model discrimination. The calibration plot and CITL confirmed reasonably good model calibration. Sensitivity and specificity were above 90% for the low and high risk levels respectively. Conclusions: We were able to validate our previously described laboratory based prognostic scoring system for COVID19 patients, to predict which patients progressed to a severe clinical course.


title: Utility of Lung Ultrasound in COVID-19: A Systematic Scoping Review

text: Lung ultrasound (LUS) has an established evidence base and has proven useful in previous viral epidemics. An understanding of the utility of LUS in COVID-19 is crucial to determine its most suitable role based on local circumstances. A scoping review was thus undertaken to explore the utility of LUS in COVID-19 and guide future research. 33 studies were identified which represent a rapidly expanding evidence base for LUS in COVID-19 however the quality of the included studies was relatively low. LUS certainly appears to be a highly sensitive and fairly specific test for COVID-19 in all ages and in pregnancy, however its accuracy may be influenced by various factors including disease severity, pre-existing lung disease, scanning protocol, operator experience, disease prevalence and the reference standard. High quality research is needed in various fields including: diagnostic accuracy in undifferentiated patients; triage and prognostication; monitoring progression and guiding interventions; persistence of residual LUS findings; inter-observer agreement; and the role of contrast-enhanced LUS.


title: Clinical Characteristics of 20,662 Patients with COVID-19 in mainland China: A Systemic Review and Meta-analysis

text: Coronavirus disease 2019 (COVID-19) is a global pandemic and has been widely reported; however, a comprehensive systemic review and meta-analysis has not been conducted. We systematically investigated the clinical characteristics of COVID-19 in mainland China to guide diagnosis and treatment. We searched the PubMed, Embase, Scopus, Web of Science, Cochrane Library, bioRxiv, medRxiv, and SSRN databases for studies related to COVID-19 published or preprinted in English or Chinese from January 1 to March 15, 2020. Clinical studies on COVID-19 performed in mainland China were included. We collected primary outcomes including signs and symptoms, chest CT imaging, laboratory tests, and treatments. Study selection, data extraction, and risk of bias assessment were performed by two independent reviewers. Qualitative and quantitative synthesis was conducted, and random-effects models were applied to pooled estimates. This study is registered with PROSPERO (number CRD42020171606). Of the 3624 records identified, 147 studies (20,662 patients) were analyzed. The mean age of patients with COVID-19 was 49.40 years, 53.45% were male, and 38.52% had at least one comorbidity. Fever and cough were the most common symptoms, followed by fatigue, expectoration, and shortness of breath. Most patients with COVID-19 had abnormal chest CT findings with ground glass opacity (70.70%) or consolidation (29.91%). Laboratory findings shown lymphopenia, increased lactate dehydrogenase, increased infection-related indicators, and fibrinolytic hyperactivity. Antiviral therapy, antibiotic therapy, and corticosteroids were administered to 89.75%, 79.13%, and 35.64% of patients, respectively. Most clinical characteristics of COVID-19 are non-specific. Patients with suspected should be evaluated by virological assays and clinically treated.


title: An inverse stage-shift model to estimate the excess mortality and health economic impact of delayed access to cancer services due to the COVID-19 pandemic

text: Background: Decreased cancer incidence and reported changes to clinical management indicate that the COVID-19 pandemic will result in diagnostic and treatment delays for cancer patients. We aimed to develop a flexible model to estimate the impact of delayed diagnosis and treatment initiation on survival outcomes and healthcare costs based on a shift in the disease stage at treatment initiation. Methods: The stage-shift model estimates population-level health economic outcomes by weighting disease stage-specific outcomes by the distribution of stages at treatment initiation, assuming delays lead to stage-progression. It allows for extrapolation of population-level survival data using parametric distributions to calculate the expected survival in life years. The model was demonstrated based on an analysis of the impact of 3 and 6-month delays for stage I breast cancer, colorectal cancer and lung cancer patients, and for T1 melanoma, based on Australian data. In the absence of patient-level data about time to stage progression, two approaches were explored to estimate the proportion of patients that would experience a stage shift following the delay: 1) based on the relation between time to treatment initiation and overall survival (breast, colorectal and lung cancer), and 2) based on the tumour growth rate (melanoma). The model is available on http://stage-shift.personex.nl/. Results: A shift from stage I to stage II due to a 6-month delay is least likely for colorectal cancer patients, with an estimated proportion of 3% of the stage I patients diagnosed in 2020 progressing to stage II, resulting in 11 excess deaths after 5 years and a total of 96 life years lost over a 10-year time horizon. For breast and lung cancer, progression from stage I to stage II due to a 6-month delay were slightly higher at 5% (breast cancer) and 8% (lung cancer), resulting in 25 and 43 excess deaths after 5 years, and 239 and 373 life years lost over a 10-year time horizon, respectively. For melanoma, with 32% of T1 patients progressing to T2 disease following a 6-month delay, the model estimated 270 excess death after 5 years and 2584 life years lost over a 10-year time horizon. Conclusions: Using a conservative 3-month delay in diagnosis and treatment initiation due to the COVID-19 pandemic, this study predicts nearly 90 excess deaths and $12 million excess healthcare costs in Australia over 5 years for the in 2020 diagnosed patients for 4 cancers. If the delays increase to 6 months, excess mortality and cost approach nearly 350 deaths and $46 million in Australia. More accurate data on stage of disease during and after the COVID-19 pandemic are critical to obtain more reliable estimates.


From the President and IFST News


title: A simple RNA preparation method for SARS-CoV-2 detection by RT-qPCR

text: The technique RT-qPCR for viral RNA detection is the current worldwide strategy used for early detection of the novel coronavirus SARS-CoV-2. RNA extraction is a key pre-analytical step in RT-qPCR, often achieved using commercial kits. However, the magnitude of the COVID-19 pandemic is causing disruptions to the global supply chains used by many diagnostic laboratories to procure the commercial kits required for RNA extraction. Shortage in these essential reagents is even more acute in developing countries with no means to produce kits locally. We sought to find an alternative procedure to replace commercial kits using common reagents found in molecular biology laboratories. Here we report a method for RNA extraction that takes about 40 min to complete ten samples and is not more laborious than current commercial RNA extraction kits. We demonstrate that this method can be used to process nasopharyngeal swab samples and yields RT-qPCR results comparable to those obtained with commercial kits. Most importantly, this procedure can be easily implemented in any molecular diagnostic laboratory. Frequent testing is crucial for individual patient management as well as for public health decision making in this pandemic. Implementation of this method could maintain crucial testing going despite commercial kit shortages.


title: Rapid detection of SARS-CoV-2 and other respiratory viruses by using LAMP method with Nanopore Flongle workflow

text: The ongoing novel coronavirus (COVID-19) outbreak as a global public health emergency infected by SARC-CoV-2 has caused devastating loss around the world. Currently, a lot of diagnosis methods have been used to detect the infection. The nucleic acid (NA) testing is reported to be the clinical standard for COVID-19 infection. Evidence shows that a faster and more convenient method to detect in the early phase will control the spreading of SARS-CoV-2. Here, we propose a method to detect SARC-Cov-2 infection within two hours combined with Loop-mediated Isothermal Amplification (LAMP) reaction and nanopore Flongle workflow. In this approach, RNA reverse transcription and nucleic acid amplification reaction with one step in 30 minutes at 60-65°C constant temperature environment, nanopore Flongle rapidly adapter ligated within 10 minutes. Flongle flow cell sequencing and analysis in real-time. This method described here has the advantages of rapid amplification, convenient operation and real-time detection which is the most important for rapid and reliable clinical diagnosis of COVID-19. Moreover, this approach not only can be used for SARS-CoV-2 detection but also can be extended to other respiratory viruses and pathogens.


title: Bibliometric analysis of corona virus research/ 冠状病毒研究的文献计量学分析

text: Objective To provide data reference for later researchers to visually and conveniently recognize the key research areas of coronavirus, quickly find important literature and influential research partners by analyzing the research literature on coronavirus. Methods Data from the Web of Science Core Collection database were selected to systematically collate the literature on coronavirus research from 1968 to 2019, and the literature type distribution, annual number of papers, countries, institutions, journals, authors, literature co citation, and emerging key words were analyzed using Microsoft Excel 2019 and CiteSpace 5.5.R2 software. Results As of December 31, 2019, a total of 13,959 papers on coronavirus have been published. Global coronavirus research is divided into three periods: The initial research period (1968-2003), the first golden development period (2004-2012) and the second golden development period (2013-2019). United States is the country with the largest number of publications; the University of Hong Kong is the institution with the largest number of publications, and the Journal of Virology ranks first in the number and influence of publications. Peiris JSM, Drosten C and Ksiazek TG are good partners in the field of coronavirus research. Conclusions "SARS-CoV", "infectious disease", "coronavirus spike protein" may attract close attention in the field of coronavirus research.


Covid-19: Testing testing


title: Seeding COVID-19 across sub-Saharan Africa: an analysis of reported importation events across 40 countries

text: Background: The first case of COVID-19 in sub-Saharan Africa (SSA) was reported by Nigeria on February 27, 2020. While case counts in the entire region remain considerably less than those being reported by individual countries in Europe, Asia, and the Americas, SSA countries remain vulnerable to significant COVID morbidity and mortality due to systemic healthcare weaknesses, less financial resources and infrastructure to address the new crisis, and untreated comorbidities. Variation in preparedness and response capacity as well as in data availability has raised concerns about undetected transmission events. Methods: Confirmed cases reported by SSA countries were line-listed to capture epidemiological details related to early transmission events into and within countries. Data were retrieved from publicly available sources, including institutional websites, situation reports, press releases, and social media accounts, with supplementary details obtained from news articles. A data availability score was calculated for each imported case in terms of how many indicators (sex, age, travel history, date of arrival in country, reporting date of confirmation, and how detected) could be identified. We assessed the relationship between time to first importation and overall Global Health Security Index (GHSI) using Cox regression. K-means clustering grouped countries according to healthcare capacity and health and demographic risk factors. Results: A total of 2417 confirmed cases of COVID-19 were reported by 40 countries in sub-Saharan Africa during the 30 days after the first known introduction to the region. Out of the 876 cases for which information was publicly available, 677 (77.3%) were considered importation events. At the regional level, imported cases tended to be male (67.3%), were a median 43.0 years old (Range: 6 weeks - 88 years), and most frequently had recent travel history from Europe (43.3%). The median time to reporting an introduction was 19 days; a country's time to report its first importation was not related to GHSI. Mean data availability scores were lowest for countries that had, on average, the highest case fatality rates, lowest healthcare capacity, and highest probability of premature death due to non-communicable diseases. Conclusion: Countries with systemic, demographic, and pre-existing health vulnerabilities to severe COVID-related morbidity and mortality are less likely to report any cases or are reporting with limited public availability of information. Reporting of information on COVID detection and response efforts, as well as on trends in non-COVID illness and care-seeking behavior, is critical to assessing direct and indirect consequences and capacity needs in resource-constrained settings. Such assessments aid in the ability to make data-driven decisions about interventions, country priorities, and risk assessment.


title: Duration of viral detection in throat and rectum of a patient with COVID-19

text: The rapid spread of coronavirus disease 2019 (COVID-19) raises concern about a global pandemic. Knowledge about the duration of viral shedding remains important for patient management and infection control. We report the duration of viral detection in throat and rectum of a COVID-19 patient treated at the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam. Despite clinical recovery, SARS-CoV-2 RNA remained detectable by real time RT-PCR in throat and rectal swabs until day 11 and 18 of hospitalization, respectively. Because live SARS-CoV-2 has been successfully isolated from a stool sample from a COVID-19 patient in China, the results demonstrate that COVID-19 patients may remain infectious for long periods, and fecal-oral transmission may be possible. Therefore, our finding has important implications for infection control.


title: Estimation of the final size of the coronavirus epidemic by the logistic model

text: In the note, the logistic growth regression model is used for the estimation of the final size and its peak time of the coronavirus epidemic. Based on available data estimation the final size will be about 90 000 cases and the peak time was on 10 Feb 2020.


Visualized effect of the Frankfurt COVid aErosol pRotEction Dome - COVERED


title: A Rapid, Cost-Effective Tailed Amplicon Method for Sequencing SARS-CoV-2

text: The global COVID-19 pandemic has led to an urgent need for scalable methods for clinical diagnostics and viral tracking. Next generation sequencing technologies have enabled large-scale genomic surveillance of SARS-CoV-2 as thousands of isolates are being sequenced around the world and deposited in public data repositories. A number of methods using both short- and long-read technologies are currently being applied for SARS-CoV-2 sequencing, including amplicon approaches, metagenomic methods, and sequence capture or enrichment methods. Given the small genome size, the ability to sequence SARS-CoV-2 at scale is limited by the cost and labor associated with making sequencing libraries. Here we describe a low-cost, streamlined, all amplicon-based method for sequencing SARS-CoV-2, which bypasses costly and time-consuming library preparation steps. We benchmark this tailed amplicon method against both the ARTIC amplicon protocol and sequence capture approaches and show that an optimized tailed amplicon approach achieves comparable amplicon balance, coverage metrics, and variant calls to the ARTIC v3 approach and represents a cost-effective and highly scalable method for SARS-CoV-2 sequencing.


title: Flattening the curve and the effect of atypical events on mitigation measures in Mexico: a modeling perspective

text: On 23 and 30 March 2020 the Mexican Federal government implemented social distancing measures to mitigate the COVID-19 epidemic. We use a mathematical model to explore atypical transmission events within the confinement period, triggered by the timing and strength of short time perturbations of social distancing. We show that social distancing measures were successful in achieving a significant reduction of the effective contact rate in the early weeks of the intervention. However, "flattening the curve" had an undesirable effect, since the epidemic peak was delayed too far, almost to the government preset day for lifting restrictions (01 June 2020). If the peak indeed occurs in late May or early June, then the events of children's day and mother's day may either generate a later peak (worst case scenario), a long plateau with relatively constant but high incidence (middle case scenario) or the same peak date as in the original baseline epidemic curve, but with a post-peak interval of slower decay.


title: The required confronting approaches efficacy and time to control COVID-19 outbreak in Iran

text: The ongoing devastating epidemic of coronavirus disease 2019 (COVID-19) in Iran and the evolving public health situation is very concerning. We have developed a deterministic epidemiological SEIR (Susceptible, Exposed, Infectious, Recovered) model to quantify the required time and efficacy to bring the COVID-19 outbreak under control in Iran. Our results showed that the efficacy of COVID-19 confronting strategies on Feb 29th and March 9th were at 0.5 and 0.7, respectively owing to the relative equivalence number of infected cases estimated by the model and national officially reported cases. Therefore, to control the COVID-19 outbreak in Iran we strongly recommend maintaining the effectiveness of interventions at 0.7 or more at least for the next 4-6 weeks. Because the COVID-19 declining statistics over the next few days or weeks do not mean the definitive control of the outbreak.


title: Isolation and chacterisation of Klebsiella phages for phage therapy

text: Klebsiella is a clinically important pathogen causing a variety of antimicrobial resistant infections, in both community and nosocomial settings, particularly pneumonia, urinary tract infection and septicaemia. We report the successful isolation and characterisation of 30 diverse Klebsiella-infecting phages. The isolated phages are diverse, spanning six different phage families and nine genera. These phages comprise of both lysogenic and lytic lifestyles. Individual Klebsiella phage isolates infected 11 of 18 different Klebsiella capsule types across all six Klebsiella species tested. Our Klebsiella-infecting lytic phages are suitable for phage therapy, based on the criteria that they encode no known toxin or antimicrobial resistance genes. However, none of the characterised phages were able to suppress the growth of Klebsiella for more than 7 hours. This indicates that for successful phage therapy, a mixed cocktail of multiple phages is necessary to treat Klebsiella infections.


title: Social Distancing Interventions in the United States: An Exploratory Investigation of Determinants and Impacts

text: Background To combat the Covid-19 pandemic in the United States, many states and Washington DC enacted Stay-at-Home order and nonpharmaceutical mitigation interventions. This study examined the determinants of the timing to implement an intervention. Through an impact analysis, the study explored the effects of the interventions and the potential risks of removing them under the context of reopening the economy. Method A content analysis identified nine types of mitigation interventions and the timing at which states enacted these strategies. A proportional hazard model, a multiple-event survival model, and a random-effect spatial error panel model in conjunction with a robust method analyzing zero-inflated and skewed outcomes were employed in the data analysis. Findings To our knowledge, we provided in this article the first explicit analysis of the timing, determinants, and impacts of mitigation interventions for all states and Washington DC in the United States during the first five weeks of the pandemic. Unlike other studies that evaluate the Stay-at-Home order by using simulated data, the current study employed the real data of various case counts of Covid-19. The study obtained two meritorious findings: (1) states with a higher prevalence of Covid-19 cases per 10,000 population reacted more slowly to the outbreak, suggesting that some states may have missed the optimal timing to prevent the wide spread of the Covid-19 disease; and (2) of nine mitigation measures, three (non-essential business closure, large-gathering bans, and restaurant/bar limitations) showed positive impacts on reducing cumulative cases, new cases, and death rates across states. Interpretation The opposite direction of the prevalence rate on the timing of issuing the mitigation interventions partially explains why the Covid-19 caseload in the U.S. remains high. A swift implementation of social distancing is crucial-the key is not whether such measures should be taken but when. Because there is no preventive vaccine and because there are few potentially effective treatments, recent reductions in new cases and deaths must be due, in large part, to the social interventions delivered by states. The study suggests that the policy of reopening economy needs to be implemented carefully.


title: Repeated seroprevalence of anti-SARS-CoV-2 IgG antibodies in a population-based sample from Geneva, Switzerland

text: Background: Assessing the burden of COVID-19 based on medically-attended case counts is suboptimal given its reliance on testing strategy, changing case definitions and the wide spectrum of disease presentation. Population-based serosurveys provide one avenue for estimating infection rates and monitoring the progression of the epidemic, overcoming many of these limitations. Methods: Taking advantage of a pool of adult participants from population-representative surveys conducted in Geneva, Switzerland, we implemented a study consisting of 8 weekly serosurveys among these participants and their household members older than 5 years. We tested each participant for anti-SARS-CoV-2-IgG antibodies using a commercially available enzyme-linked immunosorbent assay (Euroimmun AG, Lubeck, Germany). We estimated seroprevalence using a Bayesian regression model taking into account test performance and adjusting for the age and sex of Geneva's population. Results: In the first three weeks, we enrolled 1335 participants coming from 633 households, with 16% <20 years of age and 53.6% female, a distribution similar to that of Geneva. In the first week, we estimated a seroprevalence of 3.1% (95% CI 0.2-5.99, n=343). This increased to 6.1% (95% CI 2.6-9.33, n=416) in the second, and to 9.7% (95% CI 6.1-13.11, n=576) in the third week. We found that 5-19 year-olds (6.0%, 95% CI 2.3-10.2%) had similar seroprevalence to 20-49 year olds (8.5%, 95%CI 4.99-11.7), while significantly lower seroprevalence was observed among those 50 and older (3.7%, 95% CI 0.99-6.0, p=0.0008). Interpretation: Assuming that the presence of IgG antibodies is at least in the short-term associated with immunity, these results highlight that the epidemic is far from burning out simply due to herd immunity. Further, no differences in seroprevalence between children and middle age adults are observed. These results must be considered as Switzerland and the world look towards easing restrictions aimed at curbing transmission.


title: Fear of the Unknown: A Major Barrier in the New Educational Setting During the Novel Coronavirus Outbreak

text: Recently the way life is lived has undergone major changes A pandemic outbreak, caused by a new virus impacted the world in numerous ways, affecting the health system, the economy, the industry, the everyday life and last, but not least, the educational system The outbreak determined extreme measures such as school closure in the effort to contain the virus The number of individuals of all ages not attending schools or universities because of the outbreak is rising The vast majority of courses moved on-line and the e-learning represents the main educational setting used nowadays If the main disadvantages of the e-learning, mainly related to the technological features, can be overcome with the help of skills training sessions, the communication barrier caused by the fears related to this outbreak may need a different approach In this sense, the socio-constructivist theories of education, including the theories of contextualized learning all of which emphasize the socio-cultural dimension of learning, and the importance of social interactions in the process of knowledge building may represent a suitable approach


title: Physics of Virus Transmission by Speaking Droplets

text: Droplets of oral fluid emitted by speaking are a long-recognized mechanism of respiratory virus transmission. While there have been many simulations of droplet evaporation to determine whether droplets containing virions remain floating in air or rapidly fall to the ground, they typically conceal the fundamental mechanisms because of the use of numerics. To make the physics of emitted oral fluid droplets easily understood, we present simple and transparent algebraic equations that capture the essential physics of the problem. Calculations with these equations provide a straightforward way to determine the airborne lifetime of emitted droplets after accounting for the decrease in droplet size from water evaporation. At a relative humidity of 50%, droplets with initial radii larger than about 50 microns rapidly fall to the ground while smaller, potentially-virus containing droplets shrink in size and remain airborne for many minutes. Rough estimates of airborne virion emission rates while speaking support the proposal that covering the mouth can help end the pandemic more quickly.


title: Failure of the cobas(R) SARS-CoV-2 (Roche) E-gene assay is associated with a C-to-T transition at position 26340 of the SARS-CoV-2 genome

text: Control of the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic requires accurate laboratory testing to identify infected individuals, while also clearing essential staff to continue work. At the current time a number of RT-PCR tests have been developed to identify SARS-CoV-2, targeting multiple regions in the viral genome. In comparison to other RNA viruses the mutation rate of SARS-CoV-2 is moderate, however given the large number of transmission chains it is prudent to monitor circulating viruses for mutations that might compromise these tests. Here we report the identification of a C-to-T transition at position 26340 of the SARS-CoV-2 genome which is associated with failure of the cobas(R) SARS-CoV-2 E-gene assay. This variant was detected in four health care workers from the same team. Whole genome sequencing of SARS-CoV-2 showed all four to carry genetically identical viruses. Examination of viral genomes deposited on GISAID showed this mutation has arisen independently on three occasions. This work highlights the necessity of monitoring SARS-CoV-2 for the emergence of SNPs which might adversely affect the RT-PCRs used in diagnostics. Additionally, it argues that two regions in the SARS-CoV-2 should be targeted in RT-PCRs to avoid false negatives.


title: A Study of Nonstructural Protein 1 of SARS Coronavirus

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) encoded nonstructural protein 1 (nsp1) orchestrates a multi-pronged mechanism to down regulate host gene expression, also known as host shutoff Nsp1 is a 180 amino acid long protein with primarily flexible structure that allows nsp1 to interact with various cellular factors during host shutoff to inhibit translation and promote mRNA decay Mutations of the surface residues of nsp1 either attenuates or augments its host shutoff function prompting the hypothesis that these residues bind cellular proteins that facilitate nsp1 during host shutoff To identify cellular proteins that interact with nsp1 and assist its function, we conducted a quantitative proteomics experiment by comparing protein complexes associated with nsp1 and its inactive mutant (K164AH165A) and computer modeling to predict structural changes By comparing protein complexes, we identified a previously undetected mechanism by which nsp1 exploits the nuclear pore complex and disrupts nuclear-cytoplasmic transport of biomolecules Expression of nsp1 in 293 cells disrupts Nup93 localization around the nuclear envelope without triggering proteolytic degradation of the protein while other nucleoporins and the nuclear lamina remain unperturbed, suggesting a significant alteration of the nuclear pore complex in the presence of nsp1 However, expression of mutant nsp1, which does not bind to Nup93, does not alter the nuclear pore complex To better understand the structural basis of this protein?s function, we have utilized computational modeling tools, more specifically, I-TASSER (Iterative Threading ASSEmbly Refinement) Structural models of various mutants of nsp1 were obtained (by using I-TASSER) in order to explore the structural impact of different mutations Our preliminary explorations show significant topological changes on nsp1?s surface for specific mutations These perturbations of surface properties can provide a steric-based mechanism of interfering with nsp1?s binding or recognition function therefore, aggravating its host shutoff function


title: Low solid loading, low viscosity, high uniform shrinkage ceramic resin for stereolithography based additive manufacturing

text: Abstract In this work, a three-dimensional (3D) ceramic scaffold of barium titanate (BaTiO3) is realized by stereolithographic (SLA) of BaTiO3 powder and photopolymer with a high resolution and followed by a controlled thermal treatment. The photosensitive polymer in the resin mixture plays a vital role in dispersing ceramic powders and supporting complex structures cured by ultraviolet (UV) laser. The fabricated BaTiO3 and photopolymer composite part shows homogeneous dispersion of BaTiO3 microparticles. With a controlled thermal treatment, the photopolymer was carefully removed from the composite during the debinding process. Further sintering of the debinded ceramic parts at 1100 ℃, 1200 ℃, and 1300 °C shows a huge-volume shrinkage of up to 98.25% at a low concentration of ceramic powders (10 wt%). The sintered BaTiO3 ceramic parts are structurally intact with SEM images showing uniform microstructures with a relative density of 73.48%. The ultra-high shrinkage rate in this process provides a way to create complex 3D ceramic scaffolds with higher resolution than the SLA printing resolution. With the success of sintering ultralow solid loading ceramic-polymer composites, low-cost SLA 3D printers could be used to manufacture various ceramic parts with an improved resolution. This process allows widely application of 3D printed ceramics parts in the area of biomedical, aerospace, automotive, and energy fields.


title: Hydroxychloroquine and Tocilizumab Therapy in COVID-19 Patients - An Observational Study

text: Background: Hydroxychloroquine has been touted as a COVID-19 treatment. Tocilizumab, an inhibitor of IL-6, has been proposed as a treatment of critically ill patients. Objective: To describe the association between mortality and hydroxychloroquine or tocilizumab therapy among hospitalized COVID-19 patients. Design: Retrospective observational cohort study of electronic health records Setting: 13-hospital network spanning the state of New Jersey. Participants: Patients hospitalized between March 1, 2020 and April 22, 2020 with positive polymerase chain reaction results for SARS-CoV-2. Follow up was through May 5, 2020. Main Outcomes: The primary outcome was death. Results: Among 2512 hospitalized patients with COVID-19 there have been 547 deaths (22%), 1539 (61%) discharges and 426 (17%) remain hospitalized. 1914 (76%) received at least one dose of hydroxychloroquine and 1473 (59%) received hydroxychloroquine with azithromycin. After adjusting for imbalances via propensity modeling, compared to receiving neither drug, there were no significant differences in associated mortality for patients receiving any hydroxychloroquine during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]), hydroxychloroquine alone (HR, 1.02 [95% CI, 0.83-1.27]), or hydroxychloroquine with azithromycin (HR, 0.98 [95% CI, 0.75-1.28]). The 30-day unadjusted mortality for patients receiving hydroxychloroquine alone, azithromycin alone, the combination or neither drug was 25%, 20%, 18%, and 20%, respectively. Among 547 evaluable ICU patients, including 134 receiving tocilizumab in the ICU, an exploratory analysis found a trend towards an improved survival association with tocilizumab treatment (adjusted HR, 0.76 [95% CI, 0.57-1.00]), with 30 day unadjusted mortality with and without tocilizumab of 46% versus 56%. Conclusions: This observational cohort study suggests hydroxychloroquine, either alone or in combination with azithromycin, was not associated with a survival benefit among hospitalized COVID-19 patients. Tocilizumab demonstrated a trend association towards reduced mortality among ICU patients. Our findings are limited to hospitalized patients and must be interpreted with caution while awaiting results of randomized trials.


title: Spread of Covid-19 in the United States is controlled

text: As of May 1, 2020, the number of cases of Covid-19 in the US passed 1,062,446, interventions to slow down the spread of Covid-19 curtailed most social activities. Meanwhile, an economic crisis and resistance to the strict intervention measures are rising. Some researchers proposed intermittent social distancing that may drive the outbreak of Covid-19 into 2022. Questions arise about whether we should maintain or relax quarantine measures. We developed novel artificial intelligence and causal inference integrated methods for real-time prediction and control of nonlinear epidemic systems. We estimated that the peak time of the Covid-19 in the US would be April 24, 2020 and its outbreak in the US will be over by the end of July and reach 1,551,901 cases. We evaluated the impact of relaxing the current interventions for reopening economy on the spread of Covid-19. We provide tools for balancing the risks of workers and reopening economy.


Clinical characteristics of Covid-19 patients with re-positive test results: an observational study


title: Modified Vaccinia Ankara Based SARS-CoV-2 Vaccine Expressing Full-Length Spike Induces Strong Neutralizing Antibody Response

text: There is a great need for the development of vaccines for preventing SARS-CoV-2 infection and mitigating the COVID-19 pandemic. Here, we developed two modified vaccinia Ankara (MVA) based vaccines which express either a membrane anchored full-length spike protein (MVA/S) stabilized in a prefusion state or the S1 region of the spike (MVA/S1) which forms trimers and is secreted. Both immunogens contained the receptor-binding domain (RBD) which is a known target of antibody-mediated neutralization. Following immunizations with MVA/S or MVA/S1, both spike protein recombinants induced strong IgG antibodies to purified full-length SARS-CoV-2 spike protein. The MVA/S induced a robust antibody response to purified RBD, S1 and S2 whereas MVA/S1 induced an antibody response to the S1 region outside of the RBD region. Both vaccines induced an antibody response in the lung and that was associated with induction of bronchus-associated lymphoid tissue. MVA/S but not MVA/S1 vaccinated mice generated robust neutralizing antibody responses against SARS-CoV-2 that strongly correlated with RBD antibody binding titers. Mechanistically, S1 binding to ACE-2 was strong but reduced following prolonged pre-incubation at room temperature suggesting confirmation changes in RBD with time. These results demonstrate MVA/S is a potential vaccine candidate against SARS-CoV-2 infection.


"doctor, You're COVID (+)": Twenty Next Steps for Plastic Surgeons


Iranian heart association task force on cardiopulmonary resuscitation guidelines on the COVID-19 outbreak


title: PROGNOSTIC FACTORS IN SPANISH COVID-19 PATIENTS: A CASE SERIES FROM BARCELONA

text: Background In addition to the lack of COVID-19 diagnostic tests for the whole Spanish population, the current strategy is to identify the disease early to limit contagion in the community. Aim To determine clinical factors of a poor prognosis in patients with COVID-19 infection. Design and Setting Descriptive, observational, retrospective study in three primary healthcare centres with an assigned population of 100,000. Method Examination of the medical records of patients with COVID-19 infections confirmed by polymerase chain reaction. Results We included 322 patients (mean age 56.7 years, 50% female, 115 (35.7%) aged [≥] 65 years). The best predictors of ICU admission or death were greater age, male sex (OR=2.99; 95%CI=1.55 to 6.01), fever (OR=2.18; 95%CI=1.06 to 4.80), dyspnoea (OR=2.22; 95%CI=1.14 to 4.24), low oxygen saturation (OR=2.94; 95%CI=1.34 to 6.42), auscultatory alterations (OR=2.21; 95%CI=1.00 to 5.29), heart disease (OR=4.37; 95%CI=1.68 to 11.13), autoimmune disease (OR=4.03; 95%CI=1.41 to 11.10), diabetes (OR=4.00; 95%CI=1.89 to 8.36), hypertension (OR=3.92; 95%CI=2.07 to 7.53), bilateral pulmonary infiltrates (OR=3.56; 95%CI=1.70 to 7.96), elevated lactate-dehydrogenase (OR=3.02; 95%CI=1.30 to 7.68), elevated C-reactive protein (OR=2.94; 95%CI=1.47 to 5.97), elevated D-dimer (OR=2.66; 95%CI=1.15 to 6.51) and low platelet count (OR=2.41; 95%CI=1.12 to 5.14). Myalgia or artralgia (OR=0.28; 95%CI=0.10 to 0.66), dysgeusia (OR=0.28; 95%CI=0.05 to 0.92) and anosmia (OR=0.23; 95%CI=0.04 to 0.75) were protective factors. Conclusion Determining the clinical, biological and radiological characteristics of patients with suspected COVID-19 infection will be key to early treatment and isolation and the tracing of contacts.


title: Air Quality and COVID-19 Prevalence/Fatality

text: To investigate the association of real-time/observed ozone/PM2.5 levels with COVID-19 prevalence/fatality, meta-regression of data from the Northeast megalopolis was conducted. Daily Air Quality Index (AQI) values based on available ozone/PM2.5 data in these counties/cities (3/15/2020-5/31/2020) were extracted from US Environmental Protection Agency and World Air Quality Project. In each county/city, total confirmed COVID-19 cases/deaths (5/31/2020) were available from Johns Hopkins Coronavirus Resource Center, and total population was extracted from US Census Bureau. Random-effects meta-regression was performed using OpenMetaAnalyst. A meta-regression graph depicted COVID-19 prevalence and fatality (plotted as logarithm-transformed prevalence/fatality on the y-axis) as a function of mean ozone/PM2.5 AQI (plotted on the x-axis). Coefficients were not statistically significant for ozone (P = 0.212/0.814 for prevalence/fatality) and PM2.5 (P = 0.986/0.499). Although multivariable analysis had been planned, it was not performed because of non-significant covariates of interest in the univariable model. In conclusion, ozone/PM2.5 may be unassociated with COVID-19 prevalence/fatality.


title: Role of Anti-SARS-CoV-2 antibodies in different cohorts: Can they provide clues for appropriate patient triaging?

text: The emergence of coronavirus disease 2019 (COVID-19) has become a major global health crisis. Currently, diagnosis is based on molecular techniques, which detect the viral nucleic acids when present at detectable levels. The serum IgG response against SARS-CoV-2 was examined by using an ELISA-based assay. Serum samples, along with nasopharyngeal specimens were collected from various cohorts and analyzed by ELISA and rRT-PCR, respectively. A total of 167 serum samples were tested for serum IgG antibodies against SARS-CoV-2 in outpatient cohorts, 15 (8.9%) were positive by rRT-PCR and the remaining 152 (91%) were negative. We used these data to generate two different assay cutoffs for serum IgG assay and investigated percent concordance with rRT-PCR test results. The emergency department data revealed, out of 151 nasopharyngeal swabs, 4 (2.6%) were positive by rRT-PCR and 18 (11.9%) were positive for serum IgG assay. Among the 18 patients that were positive for serum IgG, 13 (72.2%) exhibited 1-3 symptoms of COVID-19 and 5 (27.7%) patients did not present with any COVID-19 related symptoms, per CDC criteria. All 4 (100%) patients that were positive by rRT-PCR had symptoms of COVID-19 disease. A longitudinal study from the inpatient population suggested there was a sharp increase in the serum IgG titers in 5 patients, a moderate increase in 1 patient and a plateau in 3 patients. Sero-prevalence of COVID-19 disease in pre-procedure patients was 5.5%. Our findings suggest serological tests can be used for appropriate patient triaging when performed as an adjunct to existing molecular testing.


title: Wisconsin April 2020 Election Not Associated with Increase in COVID-19 Infection Rates

text: Background: Wisconsin (WI) held a primary election in the midst of the COVID-19 pandemic. Live voting at polls was allowed despite concern over increasing the spread of COVID-19. In addition to 1.1 million absentee ballots cast, 453,222 persons voted live. The purpose of our study was to determine if an increase in COVID-19 activity was associated with the election. Methods: Using the voting age population for the United States (US), WI, and its 3 largest counties, and daily new COVID-19 case reports from various COVID-19 web-based dashboards, daily new case rates were calculated. With election day April 7, the incubation period included April 12-21. The new case activity in the rest of the US was compared with the Wisconsin activity during the incubation period. Results: WI daily new case rates were lower than those of the rest of the US for the 10-day period before the election and remained lower during the post exposure incubation period. The ratio of Wisconsin new case rates to US new case rates was 0.34 WI: 1 US for the 10 days leading up to the election and declined to 0.28 WI: 1 US for the 10-day post-incubation period after the election. Similar analysis for Milwaukee county showed a pre-election ratio of 1.02 Milwaukee: 1 US and after the election the ratio was 0.63 Milwaukee: 1 US. Dane county had a pre-election ratio of 0.21 Dane: 1 US case, and it fell to 0.13 Dane: 1 US after the election. Waukesha county had a pre-election ratio of 0.27 Waukesha: 1 US case and that fell to 0.19 Waukesha: 1 US after the election. Conclusions: There was no increase in COVID-19 new case daily rates observed for Wisconsin or its 3 largest counties following the election on April 7, 2020, as compared to the US, during the post-incubation interval period.


title: Comparative analyses of SAR-CoV2 genomes from different geographical locations and other coronavirus family genomes reveals unique features potentially consequential to host-virus interaction and pathogenesis

text: The ongoing pandemic of the coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). We have performed an integrated sequence-based analysis of SARS-CoV2 genomes from different geographical locations in order to identify its unique features absent in SARS-CoV and other related coronavirus family genomes, conferring unique infection, facilitation of transmission, virulence and immunogenic features to the virus. The phylogeny of the genomes yields some interesting results. Systematic gene level mutational analysis of the genomes has enabled us to identify several unique features of the SARS-CoV2 genome, which includes a unique mutation in the spike surface glycoprotein (A930V (24351C>T)) in the Indian SARS-CoV2, absent in other strains studied here. We have also predicted the impact of the mutations in the spike glycoprotein function and stability, using computational approach. To gain further insights into host responses to viral infection, we predict that antiviral host-miRNAs may be controlling the viral pathogenesis. Our analysis reveals nine host miRNAs which can potentially target SARS-CoV2 genes. Interestingly, the nine miRNAs do not have targets in SARS and MERS genomes. Also, hsa-miR-27b is the only unique miRNA which has a target gene in the Indian SARS-CoV2 genome. We also predicted immune epitopes in the genomes


title: Projecting Demand-Supply Gap of Hospital Capacity in India in the face of COVID-19 pandemic using Age-Structured Deterministic SEIR model

text: BACKGROUND: Due to uncertainties encompassing the transmission dynamics of COVID-19, mathematical models informing the trajectory of disease are being proposed throughout the world. Current pandemic is also characterized by surge in hospitalizations which has overwhelmed even the most resilient health systems. Therefore, it is imperative to assess supply side preparedness in tandem with demand projections for comprehensive outlook. OBJECTIVE: Hence, we attempted this study to forecast the demand for hospital resources for one year period and correspondingly assessed capacity and tipping points of Indian health system to absorb surges in demand due to COVID-19. METHODS: We employed age- structured deterministic SEIR model and modified it to allow for testing and isolation capacity to forecast the demand under varying scenarios. Projections for documented cases were made for varying degree of mitigation strategies of a) No-lockdown b) Moderate-lockdown c) Full-lockdown. Correspondingly, data on a) General beds b) ICU beds and c) Ventilators was collated from various government records. Further, we computed the daily turnover of each of these resources which was then adjusted for proportion of cases requiring mild, severe and critical care to arrive at maximum number of COVID-19 cases manageable by health care system of India. FINDINGS: Our results revealed pervasive deficits in the capacity of public health system to absorb surge in demand during peak of epidemic. Also, continuing strict lockdown measures was found to be ineffective in suppressing total infections significantly, rather would only push the peak by a month. However, augmented testing of 500,000 tests per day during peak (mid-July) under moderate lockdown scenario would lead to more reported cases (5,500,000-6,000,000), leading to surge in demand for hospital resources. A minimum allocation of 10% public resources and 30% private resources would be required to commensurate with demand under that scenario. However, if the testing capacity is limited by 200,000 tests per day under same scenario, documented cases would plummet by half.


title: Prevalence and Influencing Factors of Anxiety and Depression Symptoms in the First-Line Medical Staff Fighting Against COVID-19 in Gansu

text: BACKGROUND: The outbreak of novel coronavirus pneumonia (COVID-19) has brought enormous physical and psychological pressure on Chinese medical staff. It is extremely important to understand the prevalence and influencing factors of anxiety and depression symptoms in first-line anti-epidemic medical staff and their coping styles for these negative emotions. METHODS: A cross-sectional survey was conducted in Gansu (China), with a questionnaire packet which consisted of the self-rating anxiety scale (SAS), self-rating depression scale (SDS), and the simplified coping style questionnaire (SCSQ). A total of 79 doctors and 86 nurses participated in the survey. Correlation analysis was performed to explore the relationship between SAS, SDS, and SCSQ score. A linear regression model was used to determine the influencing factors for anxiety or depression symptoms. RESULTS: The prevalence rates of anxiety and depression symptoms among doctors was 11.4% and 45.6%, respectively. History of depression or anxiety (T=-2.644, p= 0.010, 95%CI: -10.514~-1.481) was shown to be a risk factor for anxiety symptoms in doctors, while being male (T=2.970, p=0.004, 95%CI: 2.667~13.521) was a protective factor for depression. The prevalence rate of anxiety and depression symptoms among nurses was 27.9% and 43.0%, respectively. History of depression or anxiety was a common risk factor for anxiety symptoms (T=-3.635, p=0.000, 95%CI: -16.360~-4.789) and depression symptoms (T=-2.835, p=0.005, 95%CI:-18.238~-3.254) in nurses. The results of partial correlation analysis (controlled for gender and history of depression or anxiety) indicated that the total score of positive coping was negatively correlated with the total score of anxiety (r=-0.182, p=0.002) and depression (r=-0.253, p=0.001). CONCLUSIONS: The first-line anti-epidemic medical staff have high anxiety and depression symptoms and adopting positive coping styles will help to improve their negative emotions.


title: Case fatality risk by age from COVID-19 in a high testing setting in Latin America: Chile, March-May, 2020

text: Background Early severity estimates of COVID-19 are critically needed to better assess the potential impact of the ongoing pandemic in different socio-demographic groups. Using real-time epidemiological data from Chile, the nation in Latin America with the highest testing rate for COVID-19, we derive delay-adjusted severity estimates by age group as of May 18th, 2020. Methods We employed statistical methods and daily series of age-stratified COVID-19 cases and deaths reported in Chile to estimate the delay-adjusted case fatality rate across six age groups. Results Our most recent estimates of the time-delay adjusted case fatality rate are 0.08% (95% Credible Interval CrI:0.04-0.13%) among persons aged 0-39, 0.61% (95%CrI:0.41-0.87%) for those aged 40-49, 1.06% (95%CrI:0.76-1.40%) for those aged 50-59, 3.79% (95%CrI:3.04-4.66%) for those aged 60-69, 12.22% (95%CrI:10.40-14.38%) for those aged 70-79, and 26.27% (95%CrI:22.95-2980%) for persons aged 80 and over. The overall time-delay adjusted case fatality rate is1.78% (95%CrI: 1.63-1.95%) across all age groups. Conclusions Severity estimates from COVID-19 in Chile indicate a disproportionate impact among seniors, especially among those aged [≥] 70 years. COVID-19 is imposing a high death toll in Latin America. Case fatality rates in Chile suggest the health system is not yet overwhelmed, but the epidemic is expanding fast.


title: Absolute quantification and degradation evaluation of SARS-CoV-2 RNA by droplet digital PCR

text: Quantifying SARS-CoV-2 infectivity, formulating well-calibrated public-health policy, and managing the safety of workplaces would all be facilitated by precise measurement of the extent to which SARS-CoV-2 RNA is present in an intact form in biological specimens and human environments. We describe assays that use digital PCR in nanoliter droplets (droplet digital PCR) to measure these properties. Such assays could be broadly deployed to inform COVID-19 epidemiology, measure symptomatic and asymptomatic infectivity, and help manage the safety of environments in which people live, move, and work.


title: Study on active compounds from Huoxiang Zhengqi Oral Liquid for prevention of coronavirus disease 2019 (COVID-19) based on network pharmacology and molecular docking/ 基于网络药理学和分子对接法探索藿香正气口服液预防新型冠状病毒肺炎（COVID-19）活性化合物研究

text: Objective: To explore the active compounds of Huoxiang Zhengqi Oral Liquid for the treatment of coronavirus desease 2019 (COVID-19) by network pharmacology and molecular docking. Methods： The chemical constituents and action targets of Atractylodes chinensis, Citrus reticulata, Magnolia officinalis, Angelica dahurica, Poria cocos, Areca catechu, Pinellia ternata, Glycyrrhiza uralensis, Pogostemon cablin and Perilla frutescens were retrieved from TCMSP. Uniprot database was used to search the corresponding genes of targets, then Cyoscape 3.7.2 software was used to construct the network of medicinal materials-compound-target (gene) for visualization; GO function enrichment analysis and KEGG pathway enrichment analysis were performed through DAVID to predict its mechanism of action, and histograms and bubble maps were plotted by Prism software and Omicshare database for visualization. Results： The network of medicinal materials-compound-target contained 10 medicinal materials, 123 compounds and 257 corresponding target genes, and the key target genes involved PTGS2, HSP90AB1, AR, CAMSAP2, PPARG, NOS2, etc. GO functional enrichment analysis resulted in 278 GO entries (P < 0.05), including 178 biological processes (BP) entries and 36 cellular component (CC) entries, and 64 molecular function (MF) entries. KEGG pathway enrichment analysis revealed that there were 119 (P < 0.05) signaling pathways involving Hepatitis B, small cell lung cancer, non-small cell lung cancer, bladder cancer, prostate cancer and T cell receptor pathways. The results of molecular docking showed that the core compounds such as quercetin, isorhamnetin, irisolidone, kaempferol, wogonin, and baicalein were similar in affinity with the COVID-19 recommended medicine. Among them, quercetin, isorhamnetin and irisolidone had the strongest affinity. Conclusion: The compounds in Huoxiang Zhengqi Oral Liquid can combine with angiotensin converting enzyme II (ACE2) binding to PTGS2, HSP90AB1, AR, CAMSAP2 and other targets to regulate multiple signaling pathways, thus exerting a preventive or therapeutic effect on COVID-19.


title: Covid 19: Where’s the strategy for testing?

text: It would be nice to be able to say otherwise, but the UK’s approach to testing in this covid-19 pandemic continues to be chaotic, centralised, commercialised, and driven by numerical targets rather than clear strategy Allan Wilson, president of the Institute of Biomedical Sciences, has called this reactive and random approach the “wild west of testing ”1 Writing for BMJ Opinion this week, Chris Ham agrees The system is far from “world beating,” and ministers must be prepared to acknowledge and learn from mistakes, he says 2 What makes matters worse is the ongoing lack of honesty The government has exaggerated the performance of its much vaunted test, track, and trace system: most …


title: Preparedness and vulnerability of African countries against introductions of 2019-nCoV

text: The novel coronavirus (2019-nCoV) epidemic has spread to 23 countries from China. Local cycles of transmission already occurred in 7 countries following case importation. No African country has reported cases yet. The management and control of 2019-nCoV introductions heavily relies on the public health capacity of a country. Here we evaluate the preparedness and vulnerability of African countries against their risk of importation of 2019-nCoV. We used data on air travel volumes departing from airports in the infected provinces in China and directed to Africa to estimate the risk of introduction per country. We determined the countries capacity to detect and respond to cases with two indicators: preparedness, using the WHO International Health Regulation Monitoring and Evaluation Framework; and vulnerability, with the Infectious Disease Vulnerability Index. Countries were clustered according to the Chinese regions contributing the most to their risk. Findings: Countries at the highest importation risk (Egypt, Algeria, Republic of South Africa) have moderate to high capacity to respond to outbreaks. Countries at moderate risk (Nigeria, Ethiopia, Sudan, Angola, Tanzania, Ghana, Kenya) have variable capacity and high vulnerability. Three clusters of countries are identified that share the same exposure to the risk originating from the provinces of Guangdong, Fujian, and Beijing, respectively. Interpretation: Several countries in Africa are stepping up their preparedness to detect and cope with 2019-nCoV importations. Resources and intensified surveillance and capacity capacity should be urgently prioritized towards countries at moderate risk that may be ill-prepared to face the importation and to limit onward transmission.


title: Medical Doctors Awareness, Perception, and Attitude towards COVID-19 in Bangladesh: A Cross sectional study

text: Objective: COVID-19 has emerged as a pandemic and during the first week of May Bangladesh has reported more than 10,000 cases. A lack of awareness and poor understanding of the disease may result in rapid transmission of the disease in Bangladesh. This study aimed to investigate the awareness, perception, and attitude towards COVID-19 among Bangladeshi medical doctors. Method: This cross sectional, web-based study was conducted with the help of an online questionnaire and sent to the doctors which comprised of a series of questions regarding demographics of the participants, symptoms and incubation period of COVID-19, mode of transmission, measures to prevent transmission, availability of training and personal protective equipment in Bangladeshi hospitals, and attitude of doctors towards the treatment of suspected patients with COVID-19. Results: Of 800 medical doctors, a total 545 completed the survey (response 68.13%). Among the participants, 52.3% were females, 72.8% were below 30 years of age, and majority (52.8%) were working outside the cities in the villages and rural areas. A total of 404 (74.1%) doctors reported the correct incubation period of COVID-19. Majority doctors were aware of the symptoms with mode of transmission of COVID-19, measures to prevent hospital transmission, along with ways of identifying suspected patients with COVID-19. However, more than 90% of the doctors reported of inadequate intensive care unit and ventilator facilities along with extreme scarcity of personal protective equipment in the hospitals. 65.7% doctors prefer avoid working with a COVID-19 patient and more than 50% doctors have expressed that they would send the suspected COVID-19 patients to designated hospitals without providing treatment. Conclusion: The health authorities should take appropriate training measures to increase the awareness of the medical doctors along with providing sufficient amount of personal protective equipment for the medical doctors and supporting staff before deploying them in hospitals.


title: Review of fluid flow and convective heat transfer within rotating disk cavities with impinging jet

text: Fluid flow and convective heat transfer in rotor-stator configurations, which are of great importance in different engineering applications, are treated in details in this review. The review focuses on convective heat transfer in predominantly outward air flow in the rotor-stator geometries with and without impinging jets and incorporates two main parts, namely, experimental/theoretical methodologies and geometries/results. Experimental methodologies include naphthalene sublimation techniques, steady state (thin layer) and transient (thermochromic liquid crystals) thermal measurements, thermocouples and infra-red cameras, hot-wire anemometry, laser Doppler and particle image velocimetry, laser plane and smoke generator. Theoretical approaches incorporate modern CFD computational tools (DNS, LES, RANS etc). Geometries and results part being mentioned starting from simple to complex elucidates cases of a free rotating disk, a single disk in the crossflow, single jets impinging onto stationary and rotating disk, rotor-stator systems without and with impinging single jets, as well as multiple jets. Conclusions to the review outline perspectives of the further extension of the investigations of different kinds of the rotor-stator systems and their applications in engineering practice.


title: Clinical Sensitivity and Interpretation of PCR and Serological COVID-19 Diagnostics for Patients Presenting to the Hospital

text: Introduction: The diagnosis of COVID-19 requires integration of clinical and laboratory data. SARS-CoV-2 diagnostic assays play a central role in diagnosis and have fixed technical performance metrics. Interpretation becomes challenging because the clinical sensitivity changes as the virus clears and the immune response emerges. Our goal was to examine the clinical sensitivity of two most common SARS-CoV-2 diagnostic test modalities, polymerase chain reaction (PCR) and serology, over the disease course to provide insight into their clinical interpretation in patients presenting to the hospital. Methods: A single-center, retrospective study. To derive clinical sensitivity of PCR, we identified 209 PCR-positive SARS-CoV-2 patients with multiple PCR test results (624 total PCR tests) and calculated daily sensitivity from date of symptom onset or first positive test. To calculate daily clinical sensitivity by serology, we utilized 157 PCR-positive patients with a total of 197 specimens tested by enzyme-linked immunosorbent assay for IgM, IgG, and IgA anti-SARS-CoV-2 antibodies. Results: Clinical sensitivity of PCR decreased with days post symptom onset with >90% clinical sensitivity during the first 5 days after symptom onset, 70-71% from days 9-11, and 30% at day 21. In contrast, serological sensitivity increased with days post symptom onset with >50% of patients seropositive by at least one antibody isotype after day 7, >80% after day 12, and 100% by day 21. Conclusion: PCR and serology are complimentary modalities that require time-dependent interpretation. Superimposition of sensitivities over time indicate that serology can function as a reliable diagnostic aid indicating recent or prior infection.


title: Bilanz 2019: Bayer

text: AbstractBeim Leverkusener Konzern Bayer entwickelte sich im Jahr 2019 das Pharmageschäft besser als die Agrarsparte Mit weniger Beschäftigten als im Jahr 2018 investierte das Unternehmen mehr in die Forschung


title: Low Covid-19 hospitalisation in Dumfries and Galloway: comparison with other Scottish health boards

text: Background Covid-19 virus activity appears to have affected some parts of the United Kingdom more than others. Dumfries and Galloway (D&G) has seen fewer hospitalised cases than predicted. We wondered whether this might be related at least in part to population density. Methods We compared Covid-19 hospitalisation rates/100,000 population in D&G with those of the other 10 mainland Scottish health boards. We chose two time points: 19th April which was the peak of the pandemic in Scotland and 15th May, seven and a half weeks after lockdown. We used chi square and odds ratios with 95% confidence intervals to test for differences in hospitalisation rates and Pearson correlation coefficient to examine the relation between hospitalisation rates and population density. Population density for each health board was provided by National Records of Scotland. Results Hospitalisation in D&G was 13.4/100,000 on 19th April, falling to 1.3/100,000 by 15th May. Corresponding hospitalisation rates in Greater Glasgow & Clyde (GGC) were 50.1/100,000 and 38.9/100,000. Compared to GGC, hospitalisation rates in D&G were 3 times lower at peak (OR 0.27, 95% CI 0.17, 0.42) and 30 times lower by 15th May (OR 0.03, 95% CI 0.01, 0.14). Hospitalisation rates for the other health boards lay in between values recorded for D&G and GGC and fell in 10 of the 11 boards between these two dates. There was a positive association between hospitalisation rate and population density (r=0.756, p=0.007 on 19th April and r=0.840, p<0.001 for 15th May). Conclusion We have confirmed there are large differences in Covid-19 hospitalisation rates across the 11 mainland Scottish health boards, that are in part related to population density. These data support a regional rather than one nation approach to easing Covid-19 restrictions.


title: Corona Virus Disease 2019 (COVID-19): Knowledge, attitudes, practices (KAP) and misconceptions in the general population of Katsina State, Nigeria

text: Abstract Introduction Over six million cases of Coronavirus Disease 2019 (COVID-19) were reported globally by the second quarter of 2020. The various forms of interventions and measures adopted to control the disease affected people's social and behavioural practices. Aim This study aims to investigate COVID-19 related knowledge, attitudes and practices (KAP) as well as misconceptions in Katsina state, one of the largest epicentres of the COVID-19 outbreak in Nigeria. Methods The study is cross-sectional survey of 722 respondents using electronic questionnaire through the WhatsApp media platform. Results One thousand five hundred (1500) questionnaires were sent to the general public with a response rate of 48% (i.e. 722 questionnaires completed and returned). Among the respondents, 60% were men, 45% were 25-39 years of age, 56% held bachelor's degree/equivalent and above and 54% were employed. The study participants correct rate in the knowledge questionnaire was 80% suggesting high knowledge on the disease. A significant correlation (P < 0.05) exists between the average knowledge score of the participants and their level of education (Kendall's tau = 0.16). Overall, most of the participants agreed that the COVID-19 will be successfully controlled (84%) and the Nigerian government will win the fight against the pandemic (71%). Men were more likely than female (P < 0.05) to have recently attended a crowded place. Being more educated (bachelor's degree or equivalent and above vs diploma or equivalent and below) is associated with good COVID-19 related practices. Among the participants, 83% held at least one COVID-19 related misconception with the most frequent being that the virus was created in a laboratory (36%). Participants with lower level of education received and trust COVID-19 related information from local radio and television stations and participants at all levels of education selected that they would trust health unit and health care workers for COVID-19 related information. Conclusion Although there is high COVID-19 related knowledge among the sample, misconceptions are widespread among the participants. These misconceptions have consequences on the short- and long-term control efforts against the disease and hence should be incorporated in targeted campaigns. Health care related personnel should be in the fore front of the campaign.


title: Ebola and Marburg virus infection in bats is controlled by a systemic response

text: The filoviruses Ebola (EBOV) and Marburg (MARV) cause fatal disease in humans and nonhuman primates but are associated with subclinical infections in bats, with Rousettus aegyptiacus (Egyptian rousette/ERB) being a natural MARV reservoir. To understand the nature of this resistance, we have analyzed the effects of filovirus infection on the transcriptomes of multiple ERB tissues. We have found that while the primary locus of infection was the liver, transcriptomic changes occurred in multiple tissues, suggesting systemic responses. The transcriptional changes are indicative of inhibition of the complement system, induction of vasodilation, changes in coagulation, modulation of iron regulation, activation of a T cell response, and converting macrophages from the M1 to M2 state. We propose that these events are facets of a systemic anti-inflammatory state that enables effective control of the infection in bats and dissecting this state can inform how to control a filovirus infection in humans.


title: Development and validation of a tool to appraise guidelines on SARS-CoV-2 infection prevention strategies in healthcare workers

text: Background: Clinical guidelines on infection prevention strategies in healthcare workers (HCWs) play an important role in protecting them during the SARS-CoV-2 pandemic. Poorly constructed guidelines that are not comprehensive and are ambiguous may compromise HCWs safety. We aimed to develop and validate a tool to appraise guidelines on infection prevention strategies in HCWs. Methods: A 3-stage, web-based, Delphi consensus-building process among a panel of diverse HCWs and healthcare managers was utilised. We validated the tool by appraising 40 international, specialty-specific and procedure-specific guidelines along with national guidelines from countries with a wide range of gross national income. Results: Overall consensus (>75%) was reached at the end of three rounds for all six domains included in the tool. The chosen domains allowed appraisal of guidelines in relation to general characteristics (domain-1), recommendations on engineering (domain-2) and administrative aspects (domain 4-6) of infection prevention, as well as personal protection equipment (PPE) use (domain-3). The appraisal tool performed well across all domains and inter-rater agreement was excellent. All included guidelines performed relatively better in domains 1-3 compared with domains 4-6 and this was more evident in guidelines originating from lower income countries. Conclusion: The guideline appraisal tool was robust and easy to use. Recommendations on engineering aspects of infection prevention, administrative measures that promote optimal PPE use and HCW wellbeing were generally lacking in assessed guidelines. This tool may enable health systems to adopt high quality HCW infection prevention guidelines during SARS-CoV-2 pandemic and may also provide a framework for future guideline development.


title: COVID-19 Knowledge Graph: a computable, multi-modal, cause-and-effect knowledge model of COVID-19 pathophysiology

text: Summary The past few weeks have witnessed a worldwide mobilization of the research community in response to the novel coronavirus (COVID-19). This global response has led to a burst of publications on the pathophysiology of the virus, yet without coordinated efforts to organize this knowledge, it can remain hidden away from individual research groups. By extracting and formalizing this knowledge in a structured and computable form, as in the form of a knowledge graph, researchers can readily reason and analyze this information on a much larger scale. Here, we present the COVID-19 Knowledge Graph, an expansive cause-and-effect network constructed from scientific literature on the new coronavirus that aims to provide a comprehensive view of its pathophysiology. To make this resource available to the research community and facilitate its exploration and analysis, we also implemented a web application and released the KG in multiple standard formats. Availability The COVID-19 Knowledge Graph is publicly available under CC-0 license at https://github.com/covid19kg and https://bikmi.covid19-knowledgespace.de. Contact alpha.tom.kodamullil@scai.fraunhofer.de Supplementary information Supplementary data are available online.


title: Chimeric synthetic reference standards enable cross-validation of positive and negative controls in SARS-CoV-2 molecular tests

text: DNA synthesis in vitro has enabled the rapid production of reference standards. These are used as controls, and allow measurement and improvement of the accuracy and quality of diagnostic tests. Current reference standards typically represent target genetic material, and act only as positive controls to assess test sensitivity. However, negative controls are also required to evaluate test specificity. Using a pair of chimeric A/B RNA standards, this allowed incorporation of positive and negative controls into diagnostic testing for the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The chimeric standards constituted target regions for RT-PCR primer/probe sets that are joined in tandem across two separate synthetic molecules. Accordingly, a target region that is present in standard A provides a positive control, whilst being absent in standard B, thereby providing a negative control. This design enables cross-validation of positive and negative controls between the paired standards in the same reaction, with identical conditions. This enables control and test failures to be distinguished, increasing confidence in the accuracy of results. The chimeric A/B standards were assessed using the US Centers for Disease Control real-time RT-PCR protocol, and showed results congruent with other commercial controls in detecting SARS CoV-2 in patient samples. This chimeric reference standard design approach offers extensive flexibility, allowing representation of diverse genetic features and distantly related sequences, even from different organisms.


title: Changes in health promoting behavior during COVID-19 physical distancing: Utilizing WHOOP data to Examine Trends in Sleep, Activity, and Cardiovascular Health.

text: The COVID-19 pandemic incited global and unprecedented restrictions on the behavior of society. The aims of this study were to quantify changes to sleep/wake behavior and exercise patterns (e.g., exercise frequency, modality, and intensity), and the subsequent impact on physiological markers of health (e.g., total sleep duration, social jet lag, resting heart rate, and heart rate variability) with the introduction of physical distancing mandates and recommendations. A retrospective analysis of 50,000 subscribers to the WHOOP platform (mean age = 36.6 {+/-} 10.5; 11,956 females, 38,044 males) was conducted covering the period from January 1st, 2020 through May 15th, 2020. In order to make robust comparisons, this time period was separated into a 68 day baseline period and a 67 day physical distancing period - with a total of 6.3 million sleeps and 4.9 million exercise sessions analyzed. As compared to baseline, during physical distancing, all subjects analyzed in this study dedicated more time to sleep (+0.21 hours), fell asleep earlier (-0.43 hours), woke up earlier (-0.29 hours), obtained more sleep (+0.19 hours) and reduced social jet lag (-0.23 hours). Subjects also increased exercise frequency by an average of 1.1% and increased exercise intensity by spending an average of 1.8% more time in the three highest heart rate zones. These changes to sleep and exercise behavior may have contributed to the observed lowered resting heart rate (-0.9 beats per minute) and increased heart rate variability (+1.3 milliseconds) during physical distancing. A potential explanation for these results is that decreases in business hours-based commitments during physical distancing may have resulted in increased opportunity to engage in exercise and prioritize sleep. Therefore, as the COVID-19 pandemic eases, maintenance of certain aspects of physical distancing (e.g., flexibility to work from home) may result in a healthier population.


title: Molecular and Functional Analysis of the Human Prothrombinase Gene (HFGL2) and Its Role in Viral Hepatitis

text: In the present studies, we report the cloning and structural characterization of the HFGL2 gene and its functional role in human fulminant hepatitis. The HFGL2 gene is approximately 7 kb in length with 2 exons. The putative promoter contains cis element consensus sequences that strongly suggest the inducibility of its expression. From the nucleotide sequence of the human gene, a 439-amino acid long protein is predicted. The overall identity between the murine fgl2 and hfgl2 coded proteins is over 70%. About 225 amino acids at the carboxyl end of these molecules are almost 90% identical, and correspond to a well-conserved fibrinogen-related domain. Both HFGL2 and FGL2 encode a type II transmembrane protein with a predicted catalytic domain toward the amino terminus of the protein. Transient transfection of Chinese hamster ovary (CHO) cells with a full-length cDNA of HFGL2 coding region resulted in high levels of prothrombinase activity. Livers from 8 patients transplanted for fulminant viral hepatitis were examined for extent of necrosis, inflammation, fibrin deposition, and HFGL2 induction. In situ hybridization showed positive staining of macrophages in areas of active hepatocellular necrosis. Fibrin stained positively in these areas and was confirmed by electron microscopy. These studies define a unique prothrombinase gene (HFGL2) and implicate its importance in the pathogenesis of fulminant viral hepatitis.


title: The impact of super-spreaders in COVID-19: mapping genome variation worldwide

text: The human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the major pandemic of the 21st century. We analyzed >4,700 SARS-CoV-2 genomes and associated meta-data retrieved from public repositories. SARS-CoV-2 sequences have a high sequence identity (>99.9%), which drops to >96% when compared to bat coronavirus. We built a mutation-annotated reference SARS-CoV-2 phylogeny with two main macro-haplogroups, A and B, both of Asian origin, and >160 sub-branches representing virus strains of variable geographical origins worldwide, revealing a uniform mutation occurrence along branches that could complicate the design of future vaccines. The root of SARS-CoV-2 genomes locates at the Chinese haplogroup B1, with a TMRCA dating to 12 November 2019 - thus matching epidemiological records. Sub-haplogroup A2a originates in China and represents the major non-Asian outbreak. Multiple founder effect episodes, most likely associated with super-spreader hosts, explain COVID-19 pandemic to a large extent.


title: SARS-CoV-2 Detection Using an Isothermal Amplification Reaction and a Rapid, Inexpensive Protocol for Sample Inactivation and Purification

text: As the current SARS-CoV-2 pandemic spreads, the need for more diagnostic capabilities is great. In order to address this need, we have developed a highly sensitive RT-LAMP assay compatible with current reagents, that utilizes a colorimetric readout in as little as 30 minutes. In addition to this, we have developed an inexpensive pipeline to further increase sensitivity without requiring highly specialized equipment. A rapid inactivation protocol capable of inactivating virions, as well as endogenous nucleases, was also developed to increase sensitivity and sample stability. This protocol, combined with our RT-LAMP assay, has a sensitivity of at least 50 viral RNA copies per microliter in a sample. To further increase the sensitivity, a purification protocol compatible with this inactivation method was developed. The inactivation and purification protocol, combined with our RT-LAMP assay, brings the sensitivity to at least 1 viral RNA copy per microliter in a sample. We hope that this inactivation and purification pipeline, which costs approximately $0.07 per sample and which uses readily available reagents, will increase the availability of SARS-CoV-2 testing, as well as expand the settings in which this testing can be performed.


title: COVID-19 Presenting as Acute Limb Ischaemia

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic that developed in late 2019 and early 2020 has caused thousands of deaths and has had an enormous impact on our health systems and economies. Coronavirus disease 2019 (COVID-19) complications include disseminated coagulation and thrombosis, but, to the best of our knowledge, the literature to date on these manifestations has been limited. Herein, we report an unusual presentation in a 43-year-old man with a medical history of diabetes and hypertension who presented with dyspnoea and acute pain in his right leg and was found to have acute limb ischaemia and diabetic ketoacidosis. Our case adds to the literature regarding arterial thrombosis in COVID-19. LEARNING POINTS: Arterial thrombosis in the form of acute limb ischaemia can occur in COVID-19. A high index of suspicion should be maintained for acute limb ischaemia, which is a vascular emergency.


title: Research on the Influence of Information Diffusion on the Transmission of the Novel Coronavirus (COVID-19)

text: With the rapid development of mobile Internet in China, the information of the epidemic is full-time and holographic, and the role of information diffusion in epidemic control is increasingly prominent. At the same time, the publicity of all kinds of big data also provides the possibility to explore the impact of media information diffusion on disease transmission. This paper explores the mechanism of the influence of information diffusion on the spread of the novel coronavirus, develops a model of the interaction between information diffusion and disease transmission based on the SIR model, and empirically tests the role and mechanism of information diffusion in the spread of COCID-19 by using econometric method. The result shows that there was a significant negative correlation between the information diffusion and the spread of the novel coronavirus; The result of robust test shows that the spread of both epidemic information and protection information hindered the further spread of the epidemic.


title: Factors linked to changes in mental health outcomes among Brazilians in quarantine due to COVID-19

text: The 2020 COVID-19 pandemic is a crisis of global proportions with a significant impact on the country of Brazil. The aims of this investigation were to track changes and risk factors for mental health outcomes during state-mandated quarantine. Adults residing in Brazil (n = 360, 37.9 years of age, 68.9% female) were surveyed at the start of quarantine and 1 month later. Outcomes assessed included perceived stress, state anxiety and depression. Aside from demographics, behaviors and attitudes assessed included exercise, diet, use of tele-psychotherapy and number of COVID-19 related risk factors, such as perceived risk of COVID-19, information overload, and feeling imprisoned. Overall, all mental health outcomes worsened from Time 1 to time 2, although there was a significant gender x time interaction for stress. 9.7% of the sample reported stress above the clinical cut-off (2 SD above mean), while 8.0% and 9.4% were above this cutoff for depression and anxiety, respectively. In repeated measures analysis, female gender, worsening diet and excess of COVID-19 information was related to all mental health outcomes. Changes in diet for the worse were associated with increases in anxiety. Exercise frequency was clearly related to state anxiety (0 days/week > 6 days/week). Those who did aerobic exercise did not have any increase in depression. Use of tele-psychotherapy predicted lower levels of depression and anxiety. In multiple regression, anxiety was predicted by the greatest number of COVID-19 specific factors. In conclusion, mental health outcomes worsened for Brazilians during the first month of quarantine and these changes are associated with a variety of risk factors.