title: Clinical characteristics associated with COVID-19 severity in California

text: Given the rapidly progressing COVID-19 pandemic, this report on a US cohort of 54 COVID-19 patients from Stanford Hospital and data regarding risk factors for severe disease obtained at initial clinical presentation is of high importance and is immediately clinically relevant. We identified low presenting oxygen saturation as predictive of severe disease outcomes, such as diagnosis of pneumonia, acute respiratory distress syndrome (ARDS), and admission to the ICU, and also replicated data from China suggesting a link between hypertension and disease severity. Clinicians will benefit by tools to rapidly risk stratify patients at presentation by likelihood of progression to severe disease.


title: A cluster of COVID-19 infections indicating person-to-person transmission among casual contacts from social gatherings: An outbreak case-contact investigation

text: SARS-CoV-2, the pathogen causing COVID-19, efficiently spreads from person to person in close contact settings. Transmission among casual contacts in settings such as during social gatherings is not well understood. We report several transmission events to both close and casual contacts from a cluster of seven COVID-19 cases occurring from mid-January to early February. A total of 539 social and family contacts of the index patient’s, including members of a two-day wedding and a family party, were contacted and screened through epidemiologic surveys. The clinical progression of all cases is described. We estimate the secondary attack rate among close contacts to be 29%(2/7) and for the casual contacts to be 0.6%(3/473). The incubation period of our case cluster was 4–12 days (median, 7 days). Transmission efficiency among close contacts was higher than among casual contacts; however, transmission from second-generation cases may help spread the virus during the incubation period.


title: Classification of COVID-19 in chest X-ray images using DeTraC deep convolutional neural network

text: Chest X-ray is the first imaging technique that plays an important role in the diagnosis of COVID-19 disease. Due to the high availability of large-scale annotated image datasets, great success has been achieved using convolutional neural networks (CNNs) for image recognition and classification. However, due to the limited availability of annotated medical images, the classification of medical images remains the biggest challenge in medical diagnosis. Thanks to transfer learning, an effective mechanism that can provide a promising solution by transferring knowledge from generic object recognition tasks to domain-specific tasks. In this paper, we validate and adapt our previously developed CNN, called Decompose, Transfer, and Compose (DeTraC), for the classification of COVID-19 chest X-ray images. DeTraC can deal with any irregularities in the image dataset by investigating its class boundaries using a class decomposition mechanism. The experimental results showed the capability of DeTraC in the detection of COVID-19 cases from a comprehensive image dataset collected from several hospitals around the world. High accuracy of 95.12% (with a sensitivity of 97.91%, a specificity of 91.87%, and a precision of 93.36%) was achieved by DeTraC in the detection of COVID-19 X-ray images from normal, and severe acute respiratory syndrome cases.


OOP burden for COVID-19-like respiratory hospitalisations varies in US


title: Public perceptions and experiences of social distancing and social isolation during the COVID-19 pandemic: A UK-based focus group study

text: OBJECTIVE: Explore the perceptions and experiences of the UK public of social distancing and social isolation measures related to the COVID-19 pandemic. DESIGN: Qualitative study comprising five focus groups carried out online during the early stages of the UK's social distancing and isolation measures (5-12 days post lockdown). SETTING: Online video-conferencing PARTICIPANTS: 27 participants, all UK residents aged 18 years and older, representing a range of gender, ethnic, age and occupational backgrounds. RESULTS: The social distancing and isolation associated with COVID-19 policy has had having substantial negative impacts on the mental health and wellbeing of the UK public within a short time of policy implementation. It has disproportionately negatively affected those in low-paid or precarious employment. Practical social and economic losses - the loss of (in-person) social interaction, loss of income and loss of structure and routine - led to psychological and emotional 'losses' - the loss of motivation, loss of meaning, and loss of self-worth. Participants reported high adherence to distancing and isolation guidelines but reported seeing or hearing of non-adherence in others. A central concern for participants was the uncertainty duration of the measures, and their ability to cope longer-term. Some participants felt they would have lingering concerns over social contact while others were eager to return to high levels of social activity. CONCLUSIONS: A rapid response is necessary in terms of public health programming to mitigate the mental health impacts of COVID-19 social distancing and isolation. Initial high levels of support for, and adherence to, social distancing and isolation is likely to wane over time, particularly where end dates are uncertain. Social distancing and isolation 'exit strategies' must account for the fact that, although some individuals will voluntarily or habitually continue to socially distance, others will seek high levels of social engagement as soon as possible.


title: Social, Financial and Psychological Stress during an Emerging Pandemic: Observations from a Population Web-Based Survey in the acute phase of the COVID-19 pandemic

text: Background Understanding the multifaceted impacts of the Coronavirus-19 (COVID-19) outbreak as it unfolds is crucial to identify the most critical needs and to inform targeted interventions. Methods This population survey study presents cohort characteristics and baseline observations linked to the acute-mid phase of the COVID-19 outbreak in terms of perceived threats and concerns, occupational and financial impacts, social impacts and stress as measured by the Cohen's Perceived Stress Scale (PSS) collected cross-sectionally between April 3 and May 15, 2020. A multivariate linear regression model was used to identify factors associated with stress changes relative to pre-outbreak estimates. Results 6,040/6,685 (90.4%) participants filled out at least 1/3 of the survey and were included in the analyses. On average, PSS scores increased from 12.9+6.8 before the outbreak to 14.9+8.3 during the outbreak (p<0.001). The independent factors associated with stress worsening were: having a mental disorder, female sex, having underage children, heavier alcohol consumption, working with the general public, shorter sleep duration, younger age, less time elapsed since the start of the outbreak, lower stress before the outbreak, worse symptoms that could be linked to COVID-19, lower coping skills, worse obsessive-compulsive symptoms related to germs and contamination, personalities loading on extraversion, conscientiousness and neuroticism, left-wing political views, worse family relationships, and spending less time exercising and doing artistic activities. Interpretation Cross-sectional analyses showed a significant increase from average low to moderate stress during the COVID-19 outbreak. Identified modifiable factors associated with an increase in stress may be informative for intervention development.


title: Multimorbidity and consultation time: a systematic review

text: Background: Multimorbidity (MM) is one of the major challenges currently facing health systems at the international level and tends to occupy a considerable part of the daily activity of physicians around the world. It is important to think about the medical approach to dealing with patients with multimorbidity in order to maximize the quality of the services provided by national health services, and thus to secure a better quality of life for these patients. Information about the time spent in a medical consultation with a patient with MM criteria is essential to better organize and deliver healthcare. As far as we know, no previous review has summarized the data relating to how having MM affects the length of the average consultation time. Objective: To review all the experimental observational studies that describe the impact of having MM on the average time of a medical consultation. Methods: This systematic review was performed considering the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guidelines for systematic reviews and meta-analysis. The systematic online searches of the Embase and PubMed databases were undertaken, from January 2000 to August 2018. The studies were independently screened by two reviewers to decide which ones met the inclusion criteria. (Kappa=0.84 and Kappa=0.82). Differing opinions were solved by a third person. This systematic review included people with MM criteria as participants (two or more chronic conditions in the same individual). The type of outcome included was explicitly defined - the length of medical appointments with patients with MM criteria. Any strategies aiming to analyse the impact of MM on the average consultation time were considered. The comparator used was the length of time of medical appointment for patients without MM criteria. Experimental and observational studies were included. Results: Of 85 articles identified, only 1 observational study was included. The study shows that there is a clear trend for patients with MM criteria to have longer consultations than patients without MM criteria (p<0.001). The global quality of this study was considered Satisfactory. Conclusions: It is imperative to study the consultation time spent on patients with MM criteria. Finding a longer consultation time indicates it is important to rethink and adapt GPs lists and time planning to be able to give better medical care to patients with MM by providing agendas that have specific times set aside for these patients and allocating enough time for every task required.


title: Preliminary evaluation of voluntary event cancellation as a countermeasure against the COVID-19 outbreak in Japan as of 11 March, 2020

text: Background: To control COVID−19 outbreak in Japan, sports and entertainment events were canceled in Japan for two weeks from 26 February to 11 March. It has been designated as voluntary event cancellation (VEC). Object: This study predicts the effectiveness of VEC enduring and after its implementation. Method: We applied a simple susceptible−infected−recovery model to data of patients with symptoms in Japan during 14 January to VEC introduction and after VEC introduction to 8 March. We adjusted the reporting delay in the latest few days. Results: Results suggest that the basic reproduction number, R0, before VEC introduced as 2.50 with a 95% confidence interval (CI) was [2.43, 2.55] and the effective reproduction number, Rv, after VEC introduced as 1. 88; its 95% CI was [1.68,2.02]. Discussion and Conclusion: Results demonstrated that VEC can reduce COVID−19 infectiousness by 35%, but R0 remains higher than one.


title: Structure of SARS-CoV-2 main protease in the apo state reveals the inactive conformation

text: Mpro is of considerable interest as a drug target in the treatment of COVID-19 since the proteolytic activity of this viral protease is essential for viral replication. Here we report the first insight of the structure Mpro for SARS-CoV-2 in the inactive conformation under conditions close to the physiological state (pH 7.5) to an overall resolution of 1.9 Å. The comparisons of Mpro in different states reveal that substrate binding site and the active site are more flexible in the inactive conformation than that in the active conformations. Notably, compared with the active conformation of the apo state structure in pH7.6 of SARS, the SARS-CoV-2 apo state is in the inactive conformation under condition close to physiological state (pH7.5). Two water molecules are present in the oxyanion hole in our apo state structure, whereas in the ligand-bound structure, water molecular is absence in the same region. This structure provides novel and important insights that have broad implications for understanding the structural basis underlying enzyme activity, and can facilitate rational, structure-based, approaches for the design of specific SARS-CoV-2 ligands as new therapeutic agents.


Deaths due to covid-19 in brazil: How many are there and which are being identified?/ Óbitos por covid-19 no brasil: Quantos e quais estamos identificando?


title: Using viral genomics to estimate undetected infections and extent of superspreading events for COVID-19

text: Asymptomatic infections and limited testing capacity have led to under-reporting of SARS-CoV-2 cases. This has hampered the ability to ascertain true infection numbers, evaluate the effectiveness of surveillance strategies, determine transmission dynamics, and estimate reproductive numbers. Leveraging both viral genomic and time series case data offers methods to estimate these parameters. Using a Bayesian inference framework to fit a branching process model to viral phylogeny and time series case data, we estimated time-varying reproductive numbers and their variance, the total numbers of infected individuals, the probability of case detection over time, and the estimated time to detection of an outbreak for 12 locations in Europe, China, and the United States. The median percentage of undetected infections ranged from 13% in New York to 92% in Shanghai, China, with the length of local transmission prior to two cases being detected ranging from 11 days (95% CI: 4-21) in California to 37 days (9-100) in Minnesota. The probability of detection was as low as 1% at the start of local epidemics, increasing as the number of reported cases increased exponentially. The precision of estimates increased with the number of full-length viral genomes in a location. The viral phylogeny was informative of the variance in the reproductive number with the 32% most infectious individuals contributing 80% of total transmission events. This is the first study that incorporates both the viral genomes and time series case data in the estimation of undetected COVID-19 infections. Our findings suggest the presence of undetected infections broadly and that superspreading events are contributing less to observed dynamics than during the SARS epidemic in 2003. This genomics-informed modeling approach could estimate in near real-time critical surveillance metrics to inform ongoing COVID-19 response efforts.


title: Mathematical Model with Social Distancing Parameter for Early Estimation of COVID-19 Spread

text: COVID-19 is well known to everyone in the world. It has spread around the world. No vaccine or antiviral treatment is available till now. COVID-19 patients are increasing day by day. All countries have adopted social distancing as a preventive measure to reduce spread. It becomes necessary to estimate the number of peoples going to be affected with COVID-19 in advance so that necessary arrangements can be done. Mathematical models are used to provide early disease estimation based on limited parameters. In the present manuscript, a novel mathematical model with a social distancing parameter has been proposed to provide early COVID-19 spread estimation. The model has been validated with real data set. It has been observed that the proposed model is more accurate in spread estimation.


title: CIGB-258 immunomodulatory peptide: a novel promising treatment for critical and severe COVID-19 patients

text: This study characterizes the first clinical application of CIGB-258 in COVID-19 patients. CIGB-258 is an immunoregulatory peptide, derived from the cellular heat shock protein 60 (HSP60). Sixteen patients with COVID-19 in serious (31%) or critical (69%) conditions were included in this study. All critically ill patients recovered from the respiratory distress condition. Two of these patients had a fatal outcome due to nosocomial infections. The five seriously ill patients considerably improved. C-reactive protein (CRP) and interleukin-6 (IL-6) levels significantly decreased during treatment. CIGB-258 seems to be an effective and safe treatment option in COVID-19 patients under cytokine storm.


title: How best to use limited tests? Improving COVID-19 surveillance in long-term care

text: Background: Long-term care facilities (LTCFs) are particularly vulnerable to nosocomial outbreaks of coronavirus disease 2019 (COVID-19), with high rates of transmission and mortality. Timely epidemiological surveillance is essential to detect and respond to outbreaks, but testing resources are highly limited in the current pandemic context. Methods: We used an individual-based transmission model to simulate COVID-19 spread along inter-individual contact networks in the LTCF setting. A range of surveillance strategies were evaluated for their ability to detect simulated outbreaks, assuming limited availability of standard RT-PCR tests. Various epidemiological scenarios were considered, including COVID-19 importation from patient transfers or staff members infected in the community. Findings: We estimated a median delay of 7 (95% uncertainty interval: 2-15) days from importation of an asymptomatic COVID-19-infected patient to first presentation of COVID-19 symptoms among any patients or staff, at which point an additional 7 (0-25) individuals were infected but did not (yet) show symptoms. Across a range of scenarios, the reference surveillance strategy (testing individuals with COVID-like symptoms with signs of severity) took a median 11-21 days to detect an outbreak. Group testing (pooling specimens from multiple individuals for a single RT-PCR test) patients and staff with any COVID-like symptoms was both the most timely and efficient strategy, detecting outbreaks up to twice as quickly as the reference, and more quickly than other considered strategies while using fewer tests. Maximizing use of available tests via testing cascades was more effective than group testing only when substantial testing resources were available (on the order of 1 test/20 beds/day). Including not merely those with symptoms but also newly admitted patients in group tests and testing cascades reduced delays in outbreak detection for LTCFs actively admitting patients potentially already infected with COVID-19. Interpretation: Improving COVID-19 surveillance can alert healthcare institutions to emerging outbreaks before they escalate, informing a need for urgent public health intervention in settings with ongoing nosocomial transmission.


title: Fatigue Performance of Direct Metal Laser Sintered Parts using Reused Metallic Feedstocks

text: Abstract Though direct cost-savings are attainable with powder reuse in additive manufacturing (AM), the use of non-virgin material has raised concerns over as-built properties. Considerable efforts to validate feedstock recycling have examined static material properties, but limited studies have assessed fatigue behavior with respect to powder reuse. Ti-6AlV-4VAl, 316L, and 17-4PH stainless-steel, and were processed using thermal and atmospheric conditions representative of industrial AM machines. Fatigue specimens were sintered with virgin or eighth reuse using a standard parameter set. Specimens were tested in rotating beam fatigue testing and the stair-case method applied. The fatigue limits of 316L, 17-4PH, and Ti-6AlV-4VAl exhibited no significant difference with respect to reuse. Density measurements confirmed no reuse-dependent behavior for the stainless steels, and Ti-6V6Al-4VAl demonstrated an improvement in bulk density. Quantification of fatigue properties as a function of reuse, supports powder reuse as a viable solution for improved metal powder-bed economics.


title: COVID-19 Outbreak Prediction with Machine Learning

text: Several outbreak prediction models for COVID-19 are being used by officials around the world to make informed-decisions and enforce relevant control measures. Among the standard models for COVID-19 global pandemic prediction, simple epidemiological and statistical models have received more attention by authorities, and they are popular in the media. Due to a high level of uncertainty and lack of essential data, standard models have shown low accuracy for long-term prediction. Although the literature includes several attempts to address this issue, the essential generalization and robustness abilities of existing models needs to be improved. This paper presents a comparative analysis of machine learning and soft computing models to predict the COVID-19 outbreak. Among a wide range of machine learning models investigated, two models showed promising results (i.e., multi-layered perceptron, MLP, and adaptive network-based fuzzy inference system, ANFIS). Based on the results reported here, and due to the highly complex nature of the COVID-19 outbreak and variation in its behavior from nation-to-nation, this study suggests machine learning as an effective tool to model the outbreak.


title: Experimental investigations into alumina ceramic micromachining by electrochemical discharge machining process

text: Abstract Alumina as a substrate is being explored in the upcoming 5th generation radio-frequency micro-electro-mechanical system (MEMS) applications due to its superior electrical insulation, excellent wear resistance, and higher thermal conductivity. However, due to its brittle nature, its micromachining capabilities by the conventional contact-based processes has remained a challenge. This work reports the fabrication of deep micro-holes in hard-to-machine alumina substrates by the electrochemical discharge machining process. The effects of machining voltage and tool feed rate on the geometrical characteristics such as depth, overcut, sidewall profile of the micro-holes along with tool wear are reported. A high carbon steel needle having a tip size of 150 µm was used as a tool electrode, and 30wt% aqueous sodium hydroxide (NaOH) was used as an electrolyte. The experimental results reveal the optimal machining performance in terms of higher depth of micro-hole, lower overcut, and minimum tool consumption at a machining voltage of 50 V and a feed rate of 0.25 µm/s. A deep micro-holes (>300 µm) were achieved at a machining voltage of 55 V using a combined feed mechanism. The experimental results were compared to the numeric results obtained by using the finite-element method. The experimental results confirmed that machining of alumina is more difficult than glass-based materials and requires higher machining voltage; however, higher tool wear takes place at higher voltage, which in turn requires the usage of tool electrodes having a higher melting point. The research outcome of this work can be used in ceramic micromachining.


Protecting Cancer Patients During the Coronavirus Pandemic


title: Differential expression of COVID-19-related genes in European Americans and African Americans

text: The Coronavirus disease 2019 (COVID-19) pandemic has affected African American populations disproportionately in regards to both morbidity and mortality. A multitude of factors likely account for this discrepancy. Gene expression represents the interaction of genetics and environment. To elucidate whether levels of expression of genes implicated in COVID-19 vary in African Americans as compared to European Americans, we re-mine The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) RNA-Seq data. Multiple genes integral to infection, inflammation and immunity are differentially regulated across the two populations. Most notably, F8A2 and F8A3, which encode the HAP40 protein that mediates early endosome movement in Huntington’s Disease, are more highly expressed by up to 24-fold in African Americans. Such differences in gene expression can establish prognostic signatures and have critical implications for precision treatment of diseases such as COVID-19. We advocate routine inclusion of information such as postal code, education level, and profession (as a proxies for socioeconomic condition) and race in the metadata about each individual sampled for sequencing studies. This relatively simple change would enable large-scale data-driven approaches to dissect relationships among race, socio-economic factors, and disease.


title: Analysis of hospitalized COVID-19 patients in the Mount Sinai Health System using electronic medical records (EMR) reveals important prognostic factors for improved clinical outcomes

text: COVID-19 is a novel threat to human health worldwide. There is an urgent need to understand patient characteristics of having COVID-19 disease and evaluate markers of critical illness and mortality. Objective: To assess association of clinical features on patient outcomes. Design, Setting, and Participants: In this observational case series, patient-level data were extracted from electronic medical records for 28,336 patients tested for SARS-CoV-2 at the Mount Sinai Health System from 2/24/ to 4/15/2020, including 6,158 laboratory-confirmed cases. Exposures: Confirmed COVID-19 diagnosis by RT-PCR assay from nasal swabs. Main Outcomes and Measures: Effects of race on positive test rates and mortality were assessed. Among positive cases admitted to the hospital (N = 3,273), effects of patient demographics, hospital site and unit, social behavior, vital signs, lab results, and disease comorbidities on discharge and death were estimated. Results: Hispanics (29%) and African Americans (25%) had disproportionately high positive case rates relative to population base rates (p<2e-16); however, no differences in mortality rates were observed in the hospital. Outcome differed significantly between hospitals (Gray's T=248.9; p<2e-16), reflecting differences in average baseline age and underlying comorbidities. Significant risk factors for mortality included age (HR=1.05 [95% CI, 1.04-1.06]; p=1.15e-32), oxygen saturation (HR=0.985 [95% CI, 0.982-0.988]; p=1.57e-17), care in ICU areas (HR=1.58 [95% CI, 1.29-1.92]; p=7.81e-6), and elevated creatinine (HR=1.75 [95% CI, 1.47-2.10]; p=7.48e-10), alanine aminotransferase (ALT) (HR=1.002, [95% CI 1.001-1.003]; p=8.86e-5) and body-mass index (BMI) (HR=1.02, [95% CI 1.00-1.03]; p=1.09e-2). Asthma (HR=0.78 [95% CI, 0.62-0.98]; p=0.031) was significantly associated with increased length of hospital stay, but not mortality. Deceased patients were more likely to have elevated markers of inflammation. Baseline age, BMI, oxygen saturation, respiratory rate, white blood cell (WBC) count, creatinine, and ALT were significant prognostic indicators of mortality. Conclusions and Relevance: While race was associated with higher risk of infection, we did not find a racial disparity in inpatient mortality suggesting that outcomes in a single tertiary care health system are comparable across races. We identified clinical features associated with reduced mortality and discharge. These findings could help to identify which COVID-19 patients are at greatest risk and evaluate the impact on survival.


title: COVID-19 Confirmed Cases and Fatalities in 883 U.S. Counties with a Population of 50,000 or More: Predictions Based on Social, Economic, Demographic Factors and Shutdown Days

text: The spread of the COVID-19 virus is highly variable among U.S. counties. Seventeen factors known or thought to be related to spread of the COVID-19 virus were studied by Poisson regression analysis of confirmed cases and deaths in 883 U.S. counties with a population of 50,000 or more as of May 31, 2020. With little exception, each factor was predictive of incidence and mortality. The regression equation can be used to identify priority locations for preventive efforts and preparation for medical care caseloads when prevention is unsuccessful. Based on the correlation of cases and deaths to days since stay-at-home orders were issued, the orders reduced the cases about 48 percent and deaths about 50 percent. Focusing preventive efforts on the more vulnerable counties may be more effective and less economically damaging than statewide shutdowns.


title: COVID-19: Public Compliance with and Public Support for Stay-at-Home Mitigation Strategies

text: Objectives: Governments worldwide have recommended unprecedented measures to mitigate the coronavirus disease 2019 (COVID-19) pandemic. As pressure mounts to scale back these measures, understanding public compliance with and priorities for COVID-19 mitigation is critical. The main aim of this study was to assess public compliance with and support for government-imposed stay-at-home orders in nations and cities with different COVID-19 infection and death rates. Design: In this cross-sectional study, questionnaires were administered to nationally representative respondents from April 2-8, 2020. Setting: Regions with different disease prevalence included two nations [the United States (US, high) and Australia (AU, low)] and two cities [New York (NY, high) and Los Angeles (LA, low)]. Participants: For adults 18 years or older residing in specified regions, eligible respondents were empaneled until representative quotas were reached for age, gender, and either race and ethnicity (US, NY, LA) or ancestry (AU), matching the 2010 US or 2016 AU census. Of 8718 eligible potential respondents, 5573 (response rate, 63.9%) completed surveys (US: 3010; NY: 507; LA: 525; AU: 1531). The median age was 47 years (range, 18-89); 3039 (54.5%) were female. Exposure: The prevalence of COVID-19 in each region (cumulative infections, deaths) as of April 8, 2020: US (458610, 15659), AU (5956, 45), NY (81803, 4571), LA (7530, 198). Main Outcomes Measures: Public compliance with and attitudes regarding government-imposed stay-at-home orders were evaluated and compared between regions. Results: Of 5573 total respondents, 4560 (81.8%) reported compliance with recommended quarantine or stay-at-home policies (range of samples, 75.5%-88.2%). Despite significant disruptions of social and work life, health, and behavior, 5022 respondents (90.1%) supported government-imposed stay-at-home orders (range of samples, 88.9%-93.1%). Of these, 90.8% believe orders should last at least three more weeks or until public health or government officials recommend, with such support spanning the political spectrum. Conclusions: Public compliance with stringent quarantine and stay-at-home policies was very high, in both highly-affected (US, NY) and minimally-affected regions (AU, LA). Despite extensive disruption of respondents′ lives, the vast majority supported continuation of long-term government-imposed stay-at-home orders. These findings have important implications for policymakers grappling with the decision as to when to lift restrictions.


title: Rats and the COVID-19 pandemic: Early data on the global emergence of rats in response to social distancing

text: Following widespread closures of food-related businesses due to efforts to curtail the spread of SARS-CoV-2, public health authorities reported increased sightings of rats in close vicinity of people. Because rats vector a number of pathogens transmissible to people, changes in their behavior has consequences for human health risks. To determine the extent of how stay-at-home measures influenced patterns of rat sightings we: 1) examined the number of rat-related public service requests before and during the period of lockdown in New York City (NYC) and Tokyo, Japan; 2) examined reports made in proximity to closed food service establishments in NYC; and 3) surveyed pest control companies in the United States, Canada, Japan, and Poland. During the month following lockdown, the overall number of reports decreased by 30% in NYC, while increasing 24% in Tokyo. However, new hotspots of 311 calls were observed in proximity of closed food service establishments in NYC; and there was a consistent positive association between kernel density estimates of food service establishments and location of 311 calls (r = 0.33 to 0.45). Similarly, more reports were observed in the restaurant-dense eastern side of Tokyo. Changes in clientele for pest control companies varied geographically, with 37% of pest-management companies surveyed in North America reporting 50-100% of their post-lockdown rat-related requests coming from new clients. In Warsaw, where there are no clusters of restaurants in densely-populated areas, there were no changes. In Tokyo, there were no changes in clients. We conclude that changes in public service calls are region-specific and localized, with increases in rat sightings more likely near restaurant-dense regions. Pest control companies surveyed in North America either lost much of their business or shifted clientele from old to new locations. We discuss possible mitigation measures including ramping up pest control during re-opening of food-related establishments and the need for citywide rodent surveillance and disease monitoring.


title: A simplified SARS-CoV-2 detection protocol for research laboratories

text: Widespread testing is required to limit the current public health crisis caused by the COVID-19 pandemic. Multiple tests protocols have been authorized by the food and drugs administration under an emergency use authorization (EUA). The majority of these protocols are based on the gold-standard RT-qPCR test pioneered by the U.S. Centers for Disease Control and Prevention. However, there is still a widespread lack of testing in the US and many of the clinical diagnostics protocols require extensive human labor and materials, such as RNA extraction kits, that could face supply shortages and present biosafety concerns. Given the need to develop alternative reagents and approaches to allow nucleic-acid testing in the face of heightened demand and potential shortages, we have developed a simplified SARS-CoV-2 testing protocol adapted for its use in laboratory research with minimal molecular biology equipment and expertise. The protocol requires minimal BSL1 biosafety level precautions and facilities.


Response to “a rejoinder to misleading articles about misleading media coverage: a case of COVID-19” by professor Stephen Pratt


title: Presence of SARS-CoV-2 reactive T cells in COVID-19 patients and healthy donors

text: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a rapidly unfolding pandemic, overwhelming health care systems worldwide1. Clinical manifestations of Corona-virus-disease 2019 (COVID-19) vary broadly, ranging from asymptomatic infection to acute respiratory failure and death2, yet the underlying physiological conditions and mechanisms for this high variability are still unknown. Also, the role of host immune responses in viral clearance and its involvement in pathogenesis remains unresolved. For SARS-CoV (2002/03), however, CD4+ T cell responses are generally associated with positive outcomes3,4, while cellular immune responses to SARS-CoV-2 have not yet been investigated. Here we describe an assay that allows direct detection and characterization of SARS-CoV-2 spike glycoprotein (S)-reactive CD4+ T cells in peripheral blood. We demonstrate the presence of S-reactive CD4+ T cells in 83% of COVID-19 patients, as well as in 34% of SARS-CoV-2 seronegative healthy donors, albeit at lower frequencies. Strikingly, in COVID-19 patients S-reactive CD4+ T cells equally targeted both N-terminal and C-terminal parts of S whereas in healthy donors S-reactive CD4+ T cells reacted almost exclusively to the Cterminal part that is a) characterized by higher homology to spike glycoprotein of human endemic "common cold" coronaviruses, and b) contains the S2 subunit of S with the cytoplasmic peptide (CP), the fusion peptide (FP), and the transmembrane domain (TM) but not the receptor-binding domain (RBD). S-reactive CD4+ T cells from COVID-19 patients were further distinct to those from healthy donors as they co-expressed higher levels of CD38 and HLA-DR, indicating their recent in vivo activation. Our study is the first to directly measure SARS-CoV-2-reactive T cell responses providing critical tools for large scale testing, in depth epitope mapping and characterization of potential cross-reactive cellular immunity to SARS-CoV-2. The presence of pre-existing SARS-CoV-2-reactive T cells in healthy donors is of high interest but larger scale prospective cohort studies are needed to assess whether their presence is a correlate of protection or pathology. Results of such studies will be key for a mechanistic understanding of the SARS-CoV-2 pandemic, adaptation of containment methods and to support vaccine development.


title: Dynamics of IgG seroconversion and pathophysiology of COVID-19 infections

text: We report dynamics of seroconversion to SARS-CoV-2 infections detected by IgG ELISA in 177 individuals diagnosed by RT-PCR. Longitudinal analysis identifies 2-7% of individuals who do not seroconvert even weeks after infection. They are younger and less severely affected than seroconverters. Higher antibody responses are associated with symptomatic disease, older age, ethnicity, increased co-morbidity and higher inflammatory markers such as C Reactive Protein. Antibody responses do not decline during follow up almost to 2 months. Serological assays increase understanding of disease severity. Their application in regular surveillance will clarify the duration and protective nature of humoral responses to SARS-CoV.


title: Measuring Icebergs: Using Different Methods to Estimate the Number of COVID-19 Cases in Portugal and Spain

text: The world is suffering from a pandemic called COVID-19, caused by the SARS-CoV-2 virus. The different national governments have problems evaluating the reach of the epidemic, having limited resources and tests at their disposal. Hence, any means to evaluate the number of persons with symptoms compatible with COVID-19 with reasonable level of accuracy is useful. In this paper we present the initial results of the @CoronaSurveys project. The objective of this project is the collection and publication of data concerning the number of people that show symptoms compatible with COVID-19 in different countries using open anonymous surveys. While this data may be biased, we conjecture that it is still useful to estimate the number of infected persons with the COVID-19 virus at a given point in time in these countries, and the evolution of this number over time. We show here the initial results of the @CoronaSurveys project in Spain and Portugal.


title: Anosmia and dysgeusia in COVID-19: A systematic review

text: Background: This systematic review had three aims: i) to determine the frequency of anosmia (or other smell disorders) and dysgeusia (or other taste disorders) in COVID-19 patients; ii) to determine whether anosmia or dysgeusia are independently associated with COVID-19 diagnosis; and iii) to determine whether anosmia or dysgeusia are prognostic factors for impaired outcomes among COVID-19 patients. Methods: On April 20 (th), 2020, we search MEDLINE, Embase, Global Health, Scopus, Web of Science and MedXriv. We used terms related to COVID-19, smell and taste disorders. We selected case series, cross-sectional, case-control and cohort studies. We included studies with COVID-19 patients describing their symptoms; studies that compared smell and taste disorders between COVID-19 patients and otherwise healthy subjects; and studies comparing smell and taste disorders between COVID-19 severe and mild/moderate cases. Because of methodological heterogeneity and the limited number of results, a qualitative synthesis is presented. Results: From 31 reports, we selected six (n=2,757). Six studies reported the proportion of smell and taste disorders among COVID-19 patients. Two reports studied whether smell and taste disorders were independently associated with COVID-19 diagnosis. No reports studied the association with impaired outcomes among COVID-19 patients. The frequency of anosmia ranged between 22%-68%. The definition of taste disorders varied greatly, with dysgeusia present in 33% and ageusia in 20%. People who reported loss of smell and taste had six-fold higher odds of being COVID-19 positive; similarly, anosmia and ageusia were associated with 10-fold higher odds of COVID-19 diagnosis. Conclusions: The frequency of smell and taste disorders is as high as other symptoms, thus, at least anosmia for which the definition was more consistent, could be included in lists of COVID-19 symptoms. Although there is promising evidence, it is premature to conclude that smell and taste disorders are strongly associated with COVID-19 diagnosis. Registration: PROSPERO CRD42020181308


title: A new role for Biofoundries in rapid prototyping, development, and validation of automated clinical diagnostic tests for SARS-CoV-2

text: The SARS-CoV-2 pandemic has shown how the rapid rise in demand for patient and community sample testing, required for tracing and containing a highly infectious disease, has quickly overwhelmed testing capability globally. With most diagnostic infrastructure dependent on specialised instruments, their exclusive reagent supplies quickly become bottlenecks in times of peak demand, creating an urgent need for novel approaches to boost testing capacity. We address this challenge by refocusing the full synthetic biology stack available at the London Biofoundry onto the development of alternative patient sample testing pipelines. We present a reagent-agnostic automated SARS-CoV-2 testing platform that can be quickly deployed and scaled, and that accepts a diverse range of reagents. Using an in-house-generated, open-source, MS2-virus-like-particle-SARS-CoV-2 standard, we validate RNA extraction and RT-qPCR workflows as well as two novel detection assays based on CRISPR-Cas and Loop-mediated isothermal Amplification (LAMP) approaches. In collaboration with an NHS diagnostic testing lab, we report the performance of the overall workflow and benchmark SARS-CoV-2 detection in patient samples via RT-qPCR, CRISPR-Cas, and LAMP against clinical test sets. The validated RNA extraction and RT-qPCR platform has been installed in NHS diagnostic labs and now contributes to increased patient sample processing in the UK while we continue to refine and develop novel high-throughput diagnostic methods. Finally, our workflows and protocols can be quickly implemented and adapted by members of the Global Biofoundry Alliance and the wider scientific and medical diagnostics community.


title: Transmission dynamics of SARS-COV-2 in China: impact of public health interventions

text: COVID-19 has become a global pandemic. However, the impact of the public health interventions in China needs to be evaluated. We established a SEIRD model to simulate the transmission trend of China. In addition, the reduction of the reproductive number was estimated under the current forty public health interventions policies. Furthermore, the infection curve, daily transmission replication curve, and the trend of cumulative confirmed cases were used to evaluate the effects of the public health interventions. Our results showed that the SEIRD curve model we established had a good fit and the basic reproductive number is 3.38 (95% CI, 3.25-3.48). The SEIRD curve show a small difference between the simulated number of cases and the actual number; the correlation index (H2) is 0.934, and the reproductive number (R) has been reduced from 3.38 to 0.5 under the current forty public health interventions policies of China. The actual growth curve of new cases, the virus infection curve, and the daily transmission replication curve were significantly going down under the current public health interventions. Our results suggest that the current public health interventions of China are effective and should be maintained until COVID-19 is no longer considered a global threat.


title: Modes of contact and risk of transmission in COVID-19 among close contacts

text: Background Rapid spread of SARS-CoV-2 in Wuhan prompted heightened surveillance in Guangzhou and elsewhere in China. Modes of contact and risk of transmission among close contacts have not been well estimated. Methods We included 4950 closes contacts from Guangzhou, and extracted data including modes of contact, laboratory testing, clinical characteristics of confirmed cases and source cases. We used logistic regression analysis to explore the risk factors associated with infection of close contacts. Results Among 4950 closes contacts, the median age was 38.0 years, and males accounted for 50.2% (2484). During quarantine period, 129 cases (2.6%) were diagnosed, with 8 asymptomatic (6.2%), 49 mild (38.0%), and 5 (3.9%) severe to critical cases. The sensitivity of throat swab was 71.32% and 92.19% at first to second PCR test. Among different modes of contact, household contacts were the most dangerous in catching with infection of COVID-19, with an incidence of 10.2%. As the increase of age for close contacts and severity of source cases, the incidence of COVID-19 presented an increasing trend from 1.8% (0-17 years) to 4.2% (60 or over years), and from 0.33% for asymptomatic, 3.3% for mild, to 6.2% for severe and critical source cases, respectively. Manifestation of expectoration in source cases was also highly associated with an increased risk of infection in their close contacts (13.6%). Secondary cases were in general clinically milder and were less likely to have common symptoms than those of source cases. Conclusions In conclusion, the proportion of asymptomatic and mild infections account for almost half of the confirmed cases among close contacts. The household contacts were the main transmission mode, and clinically more severe cases were more likely to pass the infection to their close contacts. Generally, the secondary cases were clinically milder than those of source cases.


title: Philippine Higher Education Institutions in the Time of COVID-19 Pandemic

text: The year 2020 is plagued with unprecedented problems that challenged the current global and national socio-political, economic, and educational landscapes In the time of COVID-19 pandemic, the global education system is in the process of transforming and adapting to new and challenging situations which test the conventional learning process of classroom human interaction and capitalize in virtual and online education This paper tries to elucidate how the Higher Education system of the Philippines experienced and responded to the challenge of providing alternative education and learning services during the COVID-19 pandemic This case study is divided into three parts The first part provides an analysis on the policies and guidelines implemented by the country's Commission on Higher Education The second part interrogates and reflects on the responses, challenges, and best practices employed by universities in implementing these guidelines Lastly this paper provides general recommendations and argues that Philippine Higher Education Institutions/HEIs should form an Education Continuity Plan that outlines the procedures and instructions that should be followed in the face of a pandemic


Prioritizing otological surgery during the COVID-19 pandemic


title: Preliminary Results of Seroprevalence of SARS-CoV-2 at Community Clinics in Tokyo

text: Serological evaluation with SARS-CoV-2 specific IgG antibody will be an alternative way to know the pandemic of novel coronavirus disease (COVID-19) if the capacity for diagnostic PCR test is limited. The point-of-care test to detect SARS-CoV-2 specific IgG antibody in peripheral blood (n =202) was performed in two community clinics in Tokyo, Japan. The overall positive rate of SRAS-CoV-2 IgG antibody was 5.9% (95% confidence interval[CI]: 3.1-10.1). Higher rate was observed for healthcare workers (n =55, 9.1 [3.0-20.0]). The limitation on antibody tests includes low sensitivity and potent cross-reactivity with the previous coronavirus. Robust healthcare policy to efficiently monitor COVID-19 spread is warranted in Tokyo.


title: Timing of PCR and Antibody Testing in Patients with COVID-19 associated dermatologic manifestations

text: A recent study from Spain noted 40 patients with chilblain-like lesions in suspected COVID-19.1 None tested PCR positive for SARS-CoV-2, but 30% had detectable antibodies. The rapid increase in chilblain/pernio-like cases during the COVID-19 pandemic is likely SARS-CoV-2-associated. The relationship between skin symptom onset and COVID-19 PCR/antibody test timing, however, remains uncharacterized. We established an international registry for cutaneous manifestations of COVID-19.2, 3 Providers reported time between dermatologic symptom onset and positive/negative COVID-19 laboratory results, when available. From 8 April-30 June, 2020, 906 laboratory-confirmed or suspected COVID-19 cases with dermatologic manifestations were reported, 534 of which were chilblains/pernio.3 Among PCR-tested patients, 57%(n=208) overall and 15%(n=23) of chilblains/pernio cases were PCR-positive. Antibody positivity was 37%(n=39) overall and 19%(n=15) for chilblains/pernio. We evaluated 163 patients with timing information on PCR and/or antibody testing (Table 1). For patients with suspected COVID-19 and any cutaneous manifestation, PCR-positive testing occurred median 6 (IQR 1-14) days after dermatologic symptoms started while PCR-negative testing occurred median 14 (IQR 7-24) days later. For patients with pernio/chilblains, PCR-positivity was noted 8 (IQR 5-14) days after symptoms and negativity median 14 (IQR 7-28) days later. Antibody testing (IgM or IgG) was positive median 30 (IQR 19-39) days after symptom onset for all dermatologic manifestations and 27 (IQR 24-33) days after chilblains/pernio onset. Like Hubiche et al, our data highlight the low frequency of SARS-CoV-2 PCR+ testing in COVID-19 patients with cutaneous manifestations. Positive predictive values for COVID-19 PCR are influenced by viral shedding kinetics, which are difficult to assess in non-respiratory presentations.4 Our data reveal that early PCR testing is more likely to be positive than later testing, even when date-of-onset is defined by cutaneous manifestations rather than systemic symptoms. Most COVID-19 antibody data are from systemically-ill patients; the kinetics of antibody production in mild-to-moderate COVID-19 infections remain unclear.5 Here, positive antibodies resulted median 30 days from disease onset, beyond the frequently used 14-21 day testing window. In outpatients with true infection, many factors influence the likelihood of a positive antibody result: antibody production, test availability, assay sensitivity, and timing of care-seeking in relation to symptom-onset. These variables influence our interpretation of individual test results and our understanding of the association between pernio and COVID-19. More population-level testing data is necessary to optimize diagnostic test timing. Positive identification of COVID-19 in minimally-symptomatic patients, including patients with skin findings, is critical to the public health effort.


title: COVID‐19 Pandemic and Shortage of Personal Protective Equipment in Tokyo Clinics

text: Clinicians worldwide are aware of the shortage of personal protective equipment (PPE) in their daily practice in the wake of the coronavirus disease 2019 (COVID‐19) pandemic. This PPE shortage has forced healthcare staff to reuse single‐use masks, clean face shields with bleach wipes, or use substitutes, which may expose health care workers to danger.


title: Assessing uncertainty in the rooting of the SARS-CoV-2 phylogeny

text: The rooting of the SARS-CoV-2 phylogeny is important for understanding the origin and early spread of the virus. Previously published phylogenies have used different rootings that do not always provide consistent results. We use several different strategies for rooting the SARS-CoV-2 tree and provide measures of statistical uncertainty for all methods. We show that methods based on the molecular clock tend to place the root in the B clade, while methods based on outgroup rooting tend to place the root in the A clade. The results from the two approaches are statistically incompatible, possibly as a consequence of deviations from a molecular clock or excess back-mutations. We also show that none of the methods provide strong statistical support for the placement of the root in any particular edge of the tree. Our results suggest that inferences on the origin and early spread of SARS-CoV-2 based on rooted trees should be interpreted with caution.


title: Clinical Laboratory Parameters Associated with Severe or Critical Novel Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-analysis

text: Background: To date, several clinical laboratory parameters associated with COVID-19 severity have been reported. However, these parameters have not been observed consistently across studies. The aim of this review was to assess clinical laboratory parameters which may serve as markers or predictors of severe or critical COVID-19 disease Methods: We conducted a systematic search of MEDLINE, Embase, Web of Science, CINAHL and Google Scholar databases from 2019 through April 18, 2020, and reviewed bibliographies of eligible studies, relevant systematic reviews, and the medRxiv pre-print server. We included hospital-based observational studies reporting clinical laboratory parameters of confirmed cases of COVID-19 and excluded studies having large proportions (>10%) of children and pregnant women. Two authors independently carried out screening of articles, data extraction and quality assessment. Meta-analyses were done using random effects model. Meta-median difference (MMD) and 95% confidence interval (CI) was calculated for each laboratory parameter. Results: Forty-five studies in 6 countries were included. Compared to non-severe COVID-19 cases, severe or critical COVID-19 disease was characterised by higher neutrophil count (MMD: 1.23 [95% CI: 0.58 to 1.88] x109 cells/L), and lower lymphocyte and CD4 counts with MMD (95% CI) of -0.39 (-0.47, -0.31) x109 cells/L and -204.9 (-302.6, -107.1) cells/l, respectively. Other notable results were observed for C-reactive protein (MMD: 36.97 [95% CI: 27.58, 46.35] mg/L), interleukin-6 (MMD: 17.37 [95% CI: 4.74, 30.00] pg/ml,), Troponin I (MMD: 0.01 [0.00, 0.02] ng/ml), and D-dimer (MMD: 0.65 [0.45, 0.85] mg/ml). Conclusions and Relevance: Relative to non-severe COVID-19, severe or critical COVID-19 is characterised by increased markers of innate immune response, decreased markers of adaptive immune response, and increased markers of tissue damage and major organ failure. These markers could be used to recognise severe or critical disease and to monitor clinical course of COVID-19.


title: Potential impact of Covid-19 response measures on invasive pneumococcal disease in England and Wales

text: In January 2020, the United Kingdom (UK) removed one of the two infant doses of the 13-valent pneumococcal conjugate vaccine (PCV13), leaving a single priming dose at 3 months and a 12 month booster. We modelled the potential impact on invasive pneumococcal disease (IPD) of a drop in PCV13 coverage associated with the restrictions on non-essential health care visits introduced to combat COVID-19 in the UK on 23 March 2020. Using a previously published model of pneumococcal transmission in England and Wales we simulated the impact of reducing PCV13 coverage by 50% for 3 months from 23 March without subsequent catch-up vaccination. To implement social distancing, we reduced mixing between and within age-groups by either 10% or 50%. In a sensitivity analysis we explored the effect of complete cessation of PCV13 vaccination during the lockdown and of extending its duration to 6 months. Annual numbers of IPD cases predicted by the model under different vaccination and lockdown scenarios with uncertainty intervals (UI) generated from the minimum and maximum values of the model predictions using 500 parameter sets with values within a pre-specified range of the maximum likelihood set. The model predicted that any increase in IPD cases from a reduction in PCV13 coverage would be more than offset by a reduction in pneumococcal transmission due to social distancing, with a net reduction in cumulative IPD cases (UI -1,479, -1,061, all ages) over the next five years. Similar results were obtained in the sensitivity analysis, though with a greater reduction with a 6 month lockdown. COVID-19 social distancing measures are predicted to have had a profound effect on pneumococcal transmission resulting in a reduction in pneumococcal carriage prevalence and IPD incidence over the first two years after the lockdown. Carriage studies will be informative in confirming the predicted impact of the social distancing measures after they have been lifted.


title: The global emergence of severe acute respiratory syndrome coronavirus 2 in human

text: Coronaviruses are spherical and enveloped RNA viruses that infect diverse vertebrates like mammals, birds and fish. There are five human coronavirus species and all of their origin is linked to animal like bat and rodent. The two coronavirus species, Middle East respiratory syndrome-related coronavirus and Severe acute respiratory syndrome-related coronavirus are lethal to human. In the second week of December 2019, there was an outbreak of pneumonia of unknown cause in the people associated with a seafood market in Wuhan, China. The disease was designated as coronavirus disease 2019 (COVID-19) and the virus was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of the genus Betacoronavirus. SARS-CoV-2 being highly transmissible and pathogenic, soon it has spread to 213 countries killing > 0.47 million people. The information on the research findings of SARS-CoC-2 are pouring from all over the world. In a special issue of VirusDisease, “The global emergence of coronavirus in human”, various topics relating to emergence, potential cases, transmission dynamics, diagnosis, pathogenesis, food safety, therapeutic strategies and antiviral properties of Ayurveda products are covered.


Background The dynamics of coronavirus disease 2019 (COVID-19) transmissibility after symptom onset remains unknown. Methods We conducted a prospective case-ascertained study on laboratory-confirmed COVID-19 cases and their contacts. Secondary clinical attack rate (considering symptomatic cases only) was analyzed for different exposure windows after symptom onset of index cases and for different exposure settings. Results Thirty-two confirmed patients were enrolled and 12 paired data (index-secondary cases) were identified among the 1,043 contacts. The secondary clinical attack rate was 0.9% (95% CI 0.5-1.7%). The attack rate was higher among those whose exposure to index cases started within five days of symptom onset (2.4%, 95% CI 1.1-4.5%) than those who were exposed later (zero case from 605 close contacts, 95% CI 0-0.61%). The attack rate was also higher among household contacts (13.6%, 95% CI 4.7-29.5%) and non-household family contacts (8.5%, 95% CI 2.4-20.3%) than that in healthcare or other settings. The higher secondary clinical attack rate for contacts near symptom onset remained when the analysis was restricted to household and family contacts. There was a trend of increasing attack rate with the age of contacts (p for trend < 0.001). Conclusions High transmissibility of COVID-19 near symptom onset suggests that finding and isolating symptomatic patients alone may not suffice to contain the epidemic, and more generalized social distancing measures are required. Rapid reduction of transmissibility over time implies that prolonged hospitalization of mild cases might not be necessary in large epidemics.


title: Hydrothermal Assisted Transient Jet Fusion of Ceramics: A Test Case Using Bentonite Clay

text: Abstract This paper presents a new additive manufacturing process of ceramics, named hydrothermal-assisted transient jet fusion, pairing heat and pressure in attempts to create a highly dense green part. The process utilizes water as a transient binder to fuse particles eliminating the possible contamination caused by traditional organic binders. Inkjet printing was employed to selectively deposit water into a powder bed. Bentonite clay powder was used as a model material for the study, due to its excellent solubility in water. An analysis of the effects of pressure and heat on powder fusion was completed using the compression strength as a quantitative measure. A processing map was created to provide a preliminary understanding of the relationship between the combination of heat and pressure and selective fusion of powder. Test cases were printed to show the capabilities of the developed process. A prediction of the parts compressive strength was done based on previous data collected. Results proved that an increase in temperature culminates a higher compression strength. Results also showed that an increase in pressure contributes to a postponed evaporation of water in the part; once the evaporation has taken place, a denser part has a more dramatic increase in compressive strength.


title: Comparison of severe and non-severe COVID-19 pneumonia: review and meta-analysis

text: Objective: To compare the difference between severe and non-severe COVID-19 pneumonia and figure out the potential symptoms lead to severity. Methods: Articles from PubMed, Embase, Cochrane database, and google up-to 24 February 2020 were systematically reviewed. Eighteen Literatures were identified with cases of COVID-19 pneumonia. The extracted data includes clinical symptoms, age, gender, sample size and region et al were systematic reviewed and meta analyzed. Results: 14 eligible studies including 1,424 patients were analyzed. Symptoms like fever (89.2%), cough (67.2%), fatigue (43.6%) were common, dizziness, hemoptysis, abdominal pain and conjunctival congestion/conjunctivitis were rare. Polypnea/dyspnea in severe patients were significantly higher than non-severe (42.7% vs.16.3%, P<0.0001). Fever and diarrhea were higher in severe patients(p=0.0374and0.0267). Further meta-analysis showed incidence of fever(OR1.70,95%CI 1.01-2.87), polypnea/dyspnea(OR3.53, 95%CI 1.95-6.38) and diarrhea(OR1.80,95%CI 1.06-3.03) was higher in severe patients, which meant the severe risk of patients with fever, polypnea/dyspnea, diarrhea were 1.70, 3.53, 1.80 times higher than those with no corresponding symptoms. Conclusions: Fever, cough and fatigue are common symptoms in COVID-19 pneumonia. Compared with non-severe patients, the symptoms as fever, polypnea/dyspnea and diarrhea are potential symptoms lead to severity.


title: 100 Days of COVID-19 in India: Current and Future Trends

text: COVID-19 classified under emerging infectious diseases has spread across the world resulting in many casualties India reported its first case on 30th January 2020 and has completed 100 days in this pandemic period The government of India has issued stringent guidelines and imposed a lockdown for long periods to ensure the practising of social distancing This paper reviews and discusses the current trends in the confirmed cases of India in comparison with the other prominent countries around the globe A novel approach using a sigmoid function to predict and forecast the trends for cases in India are also presented in this work By placing the current time on the sigmoid curve, forecasting the total number of confirmed cases by the end of the pandemic is made If proper measures and stringent guidelines are not followed, India may have to endure a total confirmed case of up to 4 4 lakh The prediction also suggests that 99 9% of the pandemic may end in India by 27th July 2020 The best possible approach is to undertake preventive measures by strictly adhering to the guidelines and policies set by the government Performing hand hygiene, practicing social distancing, surveillance and isolation is the only means to break the chain of transmission and control the pandemic


title: Exercising caution in correlating COVID-19 incidence and mortality rates with BCG vaccination policies due to variable rates of SARS CoV-2 testing

text: TThe Bacillus Calmette-Guerin (BCG) vaccine provides protection against tuberculosis (TB), and is proposed to provide protection to non-TB infectious diseases. The COVID-19 outbreak results from infection with the novel coronavirus SARS-CoV-2 (CoV-2) and was declared a pandemic on March 11th, 2020. We queried whether the BCG vaccine offers protection against CoV-2 infection. We observed that countries with a current universal BCG vaccination policy have a significantly lower COVID-19 incidence than countries which never had a universal BCG policy or had one in the past. However, population density, median age, TB incidence, urban population, and, most significantly, CoV-2 testing rate, were also connected with BCG policy and could potentially confound the analysis. By limiting the analysis to countries with high CoV-2 testing rates, defined as greater than 2,500 tests per million inhabitants, these parameters were no longer statistically associated with BCG policy. When analyzing only countries with high testing rates, there was no longer a significant association between the number of COVID-19 cases per million inhabitants and the BCG vaccination policy. Although preliminary, our analyses indicate that the BCG vaccination may not offer protection against CoV-2 infection. While reporting biases may confound our observations, our findings support exercising caution in determining potential correlation between BCG vaccination and COVID-19 incidence, in part due significantly lower rates of CoV-2 testing per million inhabitants in countries with current universal BCG vaccination policy.


title: A downscaling approach to compare COVID-19 count data from databases aggregated at different spatial scales

text: As the COVID-19 pandemic continues to threaten various regions around the world, obtaining accurate and reliable COVID-19 data is crucial for governments and local communities aiming at rigorously assessing the extent and magnitude of the virus spread and deploying efficient interventions. Using data reported between January and February 2020 in China, we compared counts of COVID-19 from near-real time spatially disaggregated data (city-level) with fine-spatial scale predictions from a Bayesian downscaling regression model applied to a reference province-level dataset. The results highlight discrepancies in the counts of coronavirus-infected cases at district level and identify districts that may require further investigation.


title: Detection of SARS-Coronavirus-2 in wastewater, using the existing environmental surveillance network: An epidemiological gateway to an early warning for COVID-19 in communities.

text: The ongoing COVID-19 pandemic caused by SARs-CoV-2 was considered to be transmitted person to person via droplet infections and fecal-oral transmission. To determine this, we used the existing polio environment surveillance network in Pakistan to investigate presence of SARs-CoV-2 using three commercially available kits and E-Gene detection published assay for surety and confirmatory of positivity. A Two-phase separation method is used for sample clarification and concentration. Before proceeding directly for RNA extraction, an additional high-speed centrifugation (14000Xg for 30 min) step was introduced to increase viral RNA yield resulting decrease in Cq value. A total of 78 wastewater samples collected from 38 districts across Pakistan, 74 wastewater samples from existing polio environment surveillance sites, 3 from drains of COVID-19 infected areas and 1 from COVID 19 quarantine center drainage, were tested for presence of SARs-CoV-2. 21 wastewater samples (27%) from 13 districts turned to be positive on RT-qPCR. SARs-COV-2 RNA positive samples from areas with COVID patients and COVID 19 patient quarantine center drainage strengthen the findings and use of wastewater surveillance in future. Furthermore, sequence data of partial ORF 1a generated from COVID 19 patient quarantine center drainage sample also reinforce our findings that SARs-CoV-2 can be detected in wastewater. This study finding indicates that SARs-CoV-2 detection through wastewater surveillance has an epidemiologic potential that can be used as early warning system to monitor viral tracking and circulation in cities with lower COVID-19 disease burden or heavily populated areas where door-to-door tracing may not be possible. However, attention needed on virus concentration and detection assay to increase the sensitivity. Development of highly sensitive assay will be an indicator for virus monitoring and to provide early warning signs.


title: COVID-19: Tracking the Pandemic with A Simple Curve Approximation Tool (SCAT)

text: Background In the current COVID-19 pandemic, much focus is put on 'flattening the curve'. This epidemiological 'curve' refers to the cases versus time graph, which shows the rise of a disease to its peak before descending. The aim in a pandemic is to flatten this curve by reducing the peak and spreading out the timeline. However, the models used to predict this curve are often not clearly outlined, no model parameters are given, and models are not tested against real data. This lack of detail makes it difficult to recreate the curve. What is much needed is a simple tool for approximating the curve to allow ideas to be tested and comparisons made. Methods This work presents a Simple Curve Approximation Tool (SCAT) which can be used by anyone. This tool allows the user to approximate and draw the curve and allows testing of assumptions, trajectories and the wildly varying figures reported in the media. The mathematics behind SCAT is clearly outlined here but understanding of this is not required. SCAT is provided online as a downloadable MS Excel workbook with some sample cases shown. Throughout this work, the parameters used are specified so that all results can be easily reproduced. Findings Although not intended as a prediction tool, SCAT has achieved less than 0.5 % error in short-term forward prediction. It also shows a very significant improvement on the pandemic exponential approximations found throughout media reporting. As a comparison tool, it highlights obvious differences between COVID-19 and other diseases, such as influenza, and between countries at different stages of the pandemic (China, Italy and the UK are used here for demonstration purposes). Interpretation SCAT allows for quick approximation of the curve and creates meaningful comparisons and understandable visualisations for COVID-19 and other diseases. Funding None.


title: Mutational spectra of SARS-CoV-2 orf1ab polyprotein and Signature mutations in the United States of America

text: Pandemic COVID-19 outbreak has been caused due to SARS-COV2 pathogen, resulting millions of infection and death worldwide, USA being on top at the present moment. The long, complex orf1ab polyproteins of SARS-COV2 play an important role in viral RNA synthesis. To assess the impact of mutations in this important domain, we analyzed 1134 complete protein sequences of orf1ab polyprotein from NCBI Virus database from affected patients across various states of USA from December 2019 to 25th April, 2020. Multiple sequence alignment using Clustal Omega followed by statistical significance was calculated. Four significant mutations T265I (nsp 2), P4715L (nsp 12) and P5828L and Y5865C (both at nsp 13) were identified in important non-structural proteins, which function either as replicase or helicase. A comparative analysis shows 265T>I, 5828P>L and 5865Y>C are unique to USA and not reported from Europe or Asia; while one, 4715P>L is predominant in both Europe and USA. Mutational changes in amino acids are predicted to alter structure and function of corresponding proteins, thereby it is imperative to consider the mutational spectra while designing new antiviral therapeutics targeting viral orf1ab.


title: Acute Myocardial Injury of Patients with Coronavirus Disease 2019

text: Background: Since the outbreak of the Coronavirus Disease 2019 (COVID-19) in China, respiratory manifestations of the disease have been observed. However, as a fatal comorbidity, acute myocardial injury (AMI) in COVID-19 patients has not been previously investigated in detail. We investigated the clinical characteristics of COVID-19 patients with AMI and determined the risk factors for AMI in them. Methods: We analyzed data from 53 consecutive laboratory-confirmed and hospitalized COVID-19 patients (28 men, 25 women; age, 19-81 years). We collected information on epidemiological and demographic characteristics, clinical features, routine laboratory tests (including cardiac injury biomarkers), echocardiography, electrocardiography, imaging findings, management methods, and clinical outcomes. Results: Cardiac complications were found in 42 of the 53 (79.25%) patients: tachycardia (n=15), electrocardiography abnormities (n=11), diastolic dysfunction (n=20), elevated myocardial enzymes (n=30), and AMI (n=6). All the six AMI patients were aged >60 years; five of them had two or more underlying comorbidities (hypertension, diabetes, cardiovascular diseases, and chronic obstructive pulmonary disease). Novel coronavirus pneumonia (NCP) severity was higher in the AMI patients than in patients with non-definite AMI (p<0.001). All the AMI patients required care in intensive care unit; of them, three died, two remain hospitalized. Multivariate analyses showed that C-reactive protein (CRP) levels, NCP severity, and underlying comorbidities were the risk factors for cardiac abnormalities in COVID-19 patients. Conclusions: Cardiac complications are common in COVID-19 patients. Elevated CRP levels, underlying comorbidities, and NCP severity are the main risk factors for cardiac complications in COVID-19 patients.


title: Phasic containment of COVID-19 in substantially affected states of India

text: The spread of COVID-19 epidemic in some highly-impacted Indian states displayed a characteristic sub-exponential growth projected up to 3 May 2020, as a consequence of lockdown strategies, in addition to improvement of reproduction number (R), serial interval, and daily growth rate, but not case fatality rate (CFR). The effect of COVID-19 containment was more prominent in second phase of lockdown with declining R, which was still >1, suggesting the requirement of sustained interventions for effective containment of COVID-19 pandemic in Indian context.


title: COVID-19: Unknowns in pregnancy- What a health care provider should know

text: At the end of the year 2019, a new virus emerged in Wuhan, China, known as Covid 19 spread rapidly, causing an epidemic in China and then a 2020 pandemic all over the world. This review discusses COVID-19 in pregnant women and carries information that a Health Care Provider must have.


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title: Clinical and Imaging Findings in COVID-19 Patients Complicated by Pulmonary Embolism

text: Objective: To describe clinical, and imaging findings including the evolution pattern in COVID-19 pneumonia complicated by pulmonary embolism (PE). Methods: Eleven of 1453 patients with a probable diagnosis of COVID-19 pneumonia were retrospectively selected for the presence of PE. Clinical and laboratory data were recorded. All cross-sectional CT imaging was qualitatively scored for the first 28 days after onset of symptoms. Results: Of 24 patients underwent CTA-PE, 11 were confirmed with PE. All 11 patients developed acute respiratory distress syndrome (ARDS). We observed an evolution pattern of predominant findings with ground-glass opacities (GGO) to GGO with crazy paving in 3 patients, then to consolidation with linear densities, or to reticulation in 9 patients. Lung cysts or traction bronchiectasis could be seen from day 5 to 9 after symptoms and reticulation, subpleural curvilinear lines were more common from day 20. The pulmonary opacities were predominantly peripheral in distribution with relative sparing of nondependent lungs. The severity of lung involvement was high with an average score of 9.7 in the first phase, 18 in the second phase plateauing in the next two phases, with a slight decrease to 16.9 in the late phase. The pulmonary emboli were most common in segmental and subsegmental pulmonary arteries. Conclusion: The incidence of PE among suspected patients in COVID-19 was high. Our study suggests PE may occur with increased frequency in the ARDS subgroup. The evolution of radiographic abnormalities showed a general pattern, but are also unique with more extensive lung injury and specific imaging features.


title: The COVID-19 pandemic in the ASEAN: A preliminary report on the spread, burden and medical capacities

text: Objective: To provide preliminary descriptions of the spread, burden and related medical capacity characteristics of the ASEAN countries Methods: We utilized the data from four main official databases, including WHO reports, the Statistics and Research of the Coronavirus Disease, and the Southeast Asia Program of the Center for Strategic and International Study The spread of the COVID- 19 pandemic, current burden and the COVID-19 medical response capacities were extracted before April 11, 2020 Results: As of April 13, 2020, the ASEAN countries reported 19 547 COVID-19 positive cases with 817 deaths (case-facility rate of 4 2%) Thailand was the first country in the region that reported having the COVID-19 cases, while Laos was the last to report confirmed COVID-19 cases Durations for the number of deaths to double were between 8-12 days For the testing and treatment capacities, the number of PCR tests provided to the populations was the highest in Vietnam, followed by Singapore, Malaysia, and Thailand Meanwhile, the percentage of the population being tested was the highest in Brunei (2 31%), followed by Singapore (1 30%) Conclusions: A wide range of interventions were taken into practice in response to the outbreak with an effort of curbing the rise of this pandemic However, special care should not be overlooked as the pandemic is placing a huge impact on the population and becomes increasingly unpredictable To tackle the spread of the pandemic in the region, the ASEAN countries should work together as one community to provide better responses to future pandemics and other transboundary public health challenges


title: protein-sol pKa: prediction of electrostatic frustration, with application to coronaviruses

text: Evolution couples differences in ambient pH to biological function through protonatable groups, in particular those that switch from buried to exposed and alter protonation state in doing so. We present a tool focusing on structure-based discovery and display of these groups. Since prediction of buried group pKas is computationally intensive, solvent accessibility of ionisable groups is displayed, from which the user can iteratively select pKa calculation centers. Results are color-coded, with emphasis on buried groups. Utility is demonstrated with coronaviruses, which exhibit variable dependence on the acidic pH of the endocytotic pathway. After benchmarking with variants of murine hepatitis virus, a pair of conserved histidine residues are identified that are predicted to be electrostatically frustrated at acidic pH in a common structural core of pre- and post-fusion coronavirus spike proteins. We suggest that an intermediate expanded conformation at endosomal pH could relax the frustration, allowing histidine protonation, and facilitating conformational conversion. This tool is available at http://www.protein-sol.manchester.ac.uk/pka/.


title: Clinical Characteristics of Hospitalized Patients with SARS-CoV-2 and Hepatitis B virus Co-infection

text: Background & Aims The coronavirus disease 2019 (COIVD-19) caused by SARS-CoV-2 has been characterized as a pandemic, which causes a serious public health challenge in the world. A very large group of patients infected by HBV has been reported worldwide, especially in China. In order to answer whether specific treatment strategy on the patients coinfected with HBV and SARS-CoV-2, it requires profound understanding of the clinical characteristics on those patients. However, the impacts of SARS-CoV-2 infection on HBV patients remain largely unknown. Approach & Results In this retrospective investigation, we included 123 COVID-19 patients admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, from January 5 to March 7, 2020. All enrolled patients are the laboratory confirmed COVID-19 pneumonia cases according to the criteria reported previously. A total of 123 patients were analyzed for their Clinical records, laboratory results including the diagnosis of HBV infection and liver function. Among 123 confirmed COVID-19 patients, the mean age was 51 years old and 59.3% were females (73/123). Fifteen were previously HBV infected patients, 66.7% of them were males (10/15), patients with HBV infection appeared to have a higher incidence of liver cirrhosis and an increased level of total bilirubin. Seven (46.7%) patients with HBV infection were defined as severe cases, while the severity rate was 24.1% for the patients without HBV infection (26/108). The mortality of patients with HBV infection was 13.3% (2/15) compared to 2.8% (3/108) for the patients without HBV infection. Conclusions SARS-CoV-2 infection may cause liver function damage in COVID-19 cases and the patients with HBV infection are likely to have more severe disease outcome.


Politics in Quarantine


title: A Deep Learning Algorithm for Automated Cardiac Murmur Detection Via a Digital Stethoscope Platform

text: Background There is variability among clinicians in their ability to detect murmurs during cardiac auscultation and identify the underlying pathology. Deep learning approaches have shown promise in medicine by transforming collected data into clinically significant information. Objective The objective of this research is to assess the performance of a deep learning algorithm to detect murmurs and clinically significant valvular heart disease using recordings from a commercial digital stethoscope platform. Methods Using over 34 hours of previously acquired and annotated heart sound recordings, we trained a deep neural network to detect murmurs. To test the algorithm, we enrolled 373 patients in a clinical study and collected recordings at the four primary auscultation locations. Ground truth was established using patient echocardiograms and annotations by three expert cardiologists. Results Algorithm performance for detecting murmurs has sensitivity and specificity of 76.3% and 91.4%, respectively. By omitting softer murmurs, those with grade 1, sensitivity increases to 90.0%. The algorithm detects moderate-to-severe or greater aortic stenosis with sensitivity of 97.5% and specificity of 77.7% and detects moderate-to-severe or greater mitral regurgitation with sensitivity of 64.0% and specificity of 90.5%. Conclusion The deep learning algorithm ability to detect murmurs and clinically significant aortic stenosis and mitral regurgitation is comparable to expert cardiologists. The research findings attest to the reliability and utility of such algorithms as front-line clinical support tools to aid clinicians in screening for cardiac murmurs caused by valvular heart disease.


title: Association of infected probability of COVID-19 with ventilation rates in confined spaces: a Wells-Riley equation based investigation

text: Background: A growing number of epidemiological cases are proving the possibility of airborne transmission of coronavirus disease 2019 (COVID-19). Ensuring adequate ventilation rate is essential to reduce the risk of infection in confined spaces. Methods: We obtained the quantum generation rate by a COVID-19 infector with a reproductive number based fitting approach, and then estimated the association between infected probability and ventilation rate with the Wells-Riley equation. Results: The estimated quantum generation rate of COVID-19 is 14-48 /h. To ensure infected probabolity less than 1%, ventilation rate lareger than common values (100-350 m3/h and 1200-4000 m3/h for 15 minutes and 3 hours exposure, respectively) is required. If both the infector and susceptibles wear masks, the ventilation rate ensuring less than 1% infected probability is reduced to 50-180 m3/h and 600-2000 m3/h correspondingly, which is easier to be achieved by normal ventilation mode applied in some typical scenarios, including offices, classrooms, buses and aircraft cabins. Interpretation: The risk of potential airborne transmission in confined spaces cannot be ignored. Strict preventive measures that have been widely adopted should be effective in reducing the risk of airborne transmitted infection.


The outbreak of COVID-19 in Mulhouse: Hospital crisis management and deployment of military hospital during the outbreak of COVID-19 in Mulhouse, France


Expression of Concern: Mehra MR et al. Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19. N Engl J Med. DOI: 10.1056/NEJMoa2007621.


title: Current response and management decisions of the European Union to the COVID-19 outbreak: A review

text: COVID-19 has proven to be a formidable challenge for many countries in the European Union to manage effectively. The European Union has implemented numerous strategies to face emerging issues. Member States have adopted measures such as the closure of borders and significant limitations on the mobility of people to mitigate the spread of the virus. An unprecedented crisis coordination effort between Member States has facilitated the ability to purchase equipment, personal protective equipment, and other medical supplies. Attention has also been focused on providing substantive money for research to find a vaccine and promote effective treatment therapies. Financial support has been made available to protect worker salaries and businesses to help facilitate a return to a functional economy. Lessons learned to date from COVID-19 in the European Union are many; the current crisis highlights the need to think about future pandemics from a population-based management approach and apply outside the box critical thinking. Due to the complexity, intensity, and frequency of complex disasters, global leaders in healthcare, government, and business will need to pivot from siloed approaches to decision-making to embrace multidisciplinary and transdisciplinary levels of cooperation. This cooperation requires courage and leadership to recognize that changes are necessary to avoid making the same mistakes we have planned countless times on avoiding. This study focuses on the European Union's initial response to the COVID-19 pandemic, starting with how the European Union first learned and processed the global information arising out of China, followed by the incremental population-based medicine/management decisions made that currently are defining the European Union's capacity and capability. The capacity to organize, deliver, and monitor care to a specific clinical population under a population-based management target includes strict social distancing strategies, contact testing and tracing, testing for the virus antigen and its antibodies, isolation, and treatment modalities such as new mitigating medications, and finally, a vaccine.


title: A Metapopulation Network Model for the Spreading of SARS-CoV-2: Case Study for Ireland

text: We present preliminary results on an all-Ireland network modelling approach to simulate the spreading the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2), commonly known as the coronavirus. In the model, nodes correspond to locations or communities that are connected by links indicating travel and commuting between different locations. While this proposed modelling framework can be applied on all levels of spatial granularity and different countries, we consider Ireland as a case study. The network comprises 3440 electoral divisions (EDs) of the Republic of Ireland and 890 superoutput areas (SOAs) for Northern Ireland, which corresponds to local administrative units below the NUTS 3 regions. The local dynamics within each node follows a phenomenological SIRX compartmental model including classes of Susceptibles, Infected, Recovered and Quarantined (X) inspired from Science 368, 742 (2020). For better comparison to empirical data, we extended that model by a class of Deaths. We consider various scenarios including the 5-phase roadmap for Ireland. In addition, as proof of concept, we investigate the effect of dynamic interventions that aim to keep the number of infected below a given threshold by dynamically adjusting containment measures on a national (Ireland), which could also be implemented at a regional (county) or local (ED/SOA) level.


title: S. Knobler A. Mahmoud

text: Unknown


Investigators Ramp Up Research On Loss of Smell As Early Symptom of COVID-19


title: Lung ultrasound findings in patients with novel SARS-CoV2

text: Background: Over 2 million people worldwide have been infected with Severe Acute Respiratory Distress Syndrome Corona Virus 2 (SARS CoV2). Lung ultrasound has been proposed to diagnose and it. However, little is known about ultrasound findings in these patients. Our aim is to present an overview of lung ultrasound characteristics in critically ill patients with SARS CoV2 pneumonia overall and in relation to the duration of symptoms and clinical parameters. Methods: On the Intensive Care Unit of two academic hospitals, adult patients who tested positive for SARS-CoV2 were included. Images were analyzed for pleural line characteristics, number and appearance of B-lines, BLUE-profiles (Bedside Lung Ultrasound in Emergency), pathology in the PLAPS (Postero Lateral Alveolar and Pleural Syndrome) point and a LUS-score (lung ultrasound). The primary outcomes were frequencies, percentages and differences in lung ultrasound findings overall and between short ([≤]14 days) and long (>14 days) duration of symptoms and their correlation with clinical parameters. Results: In this pilot observational study, 61 patients were included with 75 examinations for analysis. The most prevalent ultrasound findings were decreased lung sliding (36%), thickening of the pleural line (42%) and a C-profile per view (37%). Patients with ''long'' duration of symptoms presented more frequently with a thickened and irregular pleural line (21% (32) vs 9% (11), p=.01), C-profile per patient (47% (18) vs. 25% (8),p=.01) and pleural effusion (19% (14) vs 5% (3),p=.02) compared to patients with short duration of symptoms. Lung ultrasound findings did not correlate with P/F ratio, fluid balance or dynamic compliance, with the exception of the LUS-score and dynamic compliance (R2=0.27, p=.02). Conclusion: SARS CoV2 results in significant ultrasound changes, with decreased lung sliding, thickening of the pleural line and a C-profile being the most observed. With time, a thickened and irregular pleural line, C-profile and pleural effusion become more common findings.


title: A gene locus that controls expression of ACE2 in virus infection

text: The SARS-CoV-2 pandemic has resulted in widespread morbidity and mortality globally, but with widely variable outcomes. The development of severe disease and mortality is higher in older individuals, males and those with other co-morbidities, and may vary across ethnic groups. However, so far, no host genetic factor has been clearly associated with susceptibility and development of severe disease. To understand the impact of host genetics on expression of ACE2 (SARS-CoV-2 receptor) during RNA virus infection we performed a GWAS for ACE2 expression in HCV-infected liver tissue from 195 individuals. We discovered that polymorphisms in the host IFNL region which control expression of IFNL3 and IFNL4 modulate ACE2 expression. ACE2 expression was regulated additionally by age, with a subsidiary effect of co-morbidity. The IFNL locus controlled expression of a gene network incorporating many well-known interferon-stimulated genes which anti-correlated with ACE2 transcript levels. The same anti-correlation was found in the gastrointestinal tract, a site of SARS-CoV-2 replication where inflammation driven interferon-stimulated genes are negatively correlated with ACE2 expression. The interferon dependent regulation of ACE2 was identified in a murine model of SARS-CoV-1 suggesting conserved regulation of ACE2 across species. Polymorphisms in the IFNL region, as well as age, may impact not only on classical antiviral responses but also on ACE2 with potential consequences for clinical outcomes in distinct ethnic groups and with implications for therapeutic interventions.


title: Non-invasive surveys of mammalian viruses using environmental DNA

text: Environmental DNA (eDNA) and its subdiscipline, invertebrate-derived DNA (iDNA) have been used to survey biodiversity non-invasively [1,2]. Water is ubiquitous in most ecosystems, and, among invertebrates, terrestrial haematophagous leeches are abundant and can be easily collected in many tropical rainforests [3,4]. Such non-invasive nucleic acid sources can mitigate difficulties of obtaining wildlife samples, particularly in remote areas or for rare species. Recently, eDNA/iDNA sources have been applied to monitoring specific wildlife pathogens [5,6]. However, previous studies have focused on known pathogens, whereas most wildlife pathogens are uncharacterized and unknown. Non-invasive approaches to monitoring known and novel pathogens may be of particular benefit in ecosystems prone to viral emergence, many of which occur in areas where invasive sampling is challenging, such as tropical rainforests. Here, we show that both eDNA from natural waterholes, and iDNA from terrestrial haematophagous leeches, can be used to detect unknown viruses circulating in mammalian hosts (Figure 1). Using a curated set of RNA oligonucleotides based on the ViroChip microarray assay [7] as baits in a hybridization capture system, multiple mammalian RNA and DNA viruses were detected from both eDNA and iDNA samples. Congruence was found between host DNA assignment and viruses identified in leeches, and between animals observed visiting the waterholes and the viruses detected. Our results demonstrate that eDNA/iDNA samples may represent an effective non-invasive resource for studying wildlife viral diversity. Several of the detected viruses were novel, highlighting the potential of eDNA/iDNA for epidemiological analysis of emerging viruses prior to their emergence. Highlights Environmental DNA (water and blood-sucking leeches) provided a non-invasive method of screening wildlife for viruses A comprehensive viral RNA oligonucleotide bait set was developed to capture known and unknown mammalian virus diversity Leech blood meal host determination and viruses identified were congruent Viruses determined from water correlated with known and observed species visiting the water sources In brief Alfano, Dayaram, et al. demonstrate that environmental DNA from southeast Asian leech bloodmeals and waterholes from Africa and Mongolia can be used as to detect viruses circulating in wildlife. These nucleic acid sources may represent an effective non-invasive resource for studying wildlife viral diversity and emerging viruses pre-emergence.


title: Professional social media usage: Work engagement perspective

text: Social media enables information sharing and social interaction within organization. This research aims to analyze how both work- and nonwork-related communication with colleagues and the work community on social media is associated with work engagement among Finnish professionals. A total of five Finnish professional organizations (N = 563) and a representative sample of the Finnish working population (N = 1817) contributed to the survey data, which was analyzed with structural equation modeling. We found a direct positive association between work-related communication and work engagement among Finnish working population, and a positive indirect associations between both work- and nonwork-related communication and work engagement via organizational identification and social support. Findings suggest that communication in social media supports work engagement via organizational identification and social support. Organizations should pay more attention to social media communication practices and provide opportunities to build organizational identification and receive social support in social media.


title: The epidemiologic parameters for COVID-19: A Systematic Review and Meta-Analysis

text: Introduction: The World Health Organization (WHO) declared the outbreak to be a public health emergency and international concern and recognized it as a pandemic. The aim of this study was to estimate the epidemiologic parameters of novel coronavirus (COVID-19) pandemic for clinical and epidemiological help. Methods: Four electronic databases including Web of Science, Medline (PubMed), Scopus and Google Scholar were searched for literature published from early December 2019 up to 23 March 2020. The "metan" command was used to perform a fixed or random effects analysis. Cumulative meta-analysis was performed using the "metacum" command. Results: Totally 76 observational studies were included in the analysis. The pooled estimate for R0 was 2.99 (95% CI: 2.71-3.27) for COVID-19. The overall R0 was 3.23, 1.19, 3.6 and 2.35 for China, Singapore, Iran and Japan, respectively. The overall Serial Interval, doubling time, incubation period were 4.45, 4.14 and 4.24 days for COVID-19. In addition, the overall estimation for growth rate and case fatality rate for COVID-19 were 0.38% and 3.29%, respectively. Conclusion: Calculating the pooled estimate of the epidemiological parameters of COVID-19 as an emerging disease, could reveal epidemiological features of the disease that consequently pave the way for health policy makers to think more about control strategies. Keywords: Epidemiologic Parameters; R0; Serial Interval; Doubling Time; Case Fatality Rate;COVID-19