title: Dynamics of the upper airway microbiome in the pathogenesis of asthma-associated persistent wheeze in preschool children

text: Repeated cycles of infection-associated lower airway inflammation drives the pathogenesis of persistent wheezing disease in children. Tracking these events across a birth cohort during their first five years, we demonstrate that >80% of infectious events indeed involve viral pathogens, but are accompanied by a shift in the nasopharyngeal microbiome (NPM) towards dominance by a small range of pathogenic bacterial genera. Unexpectedly, this change in NPM frequently precedes the appearance of viral pathogens and acute symptoms. In non-sensitized children these events are associated only with “transient wheeze” that resolves after age three. In contrast, in children developing early allergic sensitization, they are associated with ensuing development of persistent wheeze, which is the hallmark of the asthma phenotype. This suggests underlying pathogenic interactions between allergic sensitization and antibacterial mechanisms.


title: CoViD-19 outbreak in Northern Italy: Did particulate matter really play a key role?

text: Northern Italian regions have been the most affected from CoViD-19 compared to other Italian areas and are also the zones where air pollutants concentration has been higher than in the rest of Italy. The aim of the research is analysing possible correlations between air pollutants PM10 and PM2.5 and the rapidity of the spread of the infection caused by CoViD-19 in Northern Italy. PM10 and PM2.5 data for all the 41 studied cities were collected from the local environmental protection agencies. In order to compare air quality data with epidemiological data (Td), a statistical analysis was conducted identifying the correlation matrices of Pearson and Spearman, considering the possible incubation period of the disease. The results exclude a strong direct correlation between PM in the air and the diffusion rate of CoViD-19. Further developments are necessary for a better comprehension of the influence of atmospheric pollution parameters on the rapidity of spread of the virus SARS-CoV-2, since a synergistic action with other factors, such as meteorological factors, could not be excluded.


title: Exposure to cough aerosols and development of pulmonary COVID-19

text: Half a year after the emergence of COVID-19, research is still going on to gain insight in the importance of different SARS-CoV-2 transmission routes and their impact on the clinical picture of COVID-19. Our findings suggest that coughing is not as important for transmission as initially anticipated and we discuss the potentially important role for loud conversation as a driver for transmission.


title: Fear can be more harmful than the severe acute respiratory syndrome coronavirus 2 in controlling the corona virus disease 2019 epidemic

text: The current corona virus disease 2019 outbreak caused by severe acute respiratory syndrome coronavirus 2 started in Wuhan, China in December 2019 and has put the world on alert. To safeguard Chinese citizens and to strengthen global health security, China has made great efforts to control the epidemic. Many in the global community have joined China to limit the epidemic. However, discrimination and prejudice driven by fear or misinformation have been flowing globally, superseding evidence and jeopardizing the anti-severe acute respiratory syndrome coronavirus 2 efforts. We analyze this phenomenon and its underlying causes and suggest practical solutions.


title: Appendix 3 The History of Virology

text: Unknown


title: Systemic corticosteroids show no benefit in severe and critical COVID-19 patients in Wuhan, China: A retrospective cohort study

text: Background: Systemic corticosteroids are recommended by some treatment guidelines and used in severe and critical COVID-19 patients, though evidence supporting such use is limited. Methods: From December 26, 2019 to March 15, 2020, 1514 severe and 249 critical hospitalized COVID-19 patients were collected from two medical centers in Wuhan, China. We performed multivariable Cox models, Cox model with time-varying exposure and propensity score analysis (both inverse-probability-of-treatment-weighting (IPTW) and propensity score matching (PSM)) to estimate the association of corticosteroid use with the risk of in-hospital mortality among severe and critical cases. Results: Corticosteroids were administered in 531 (35.1%) severe and 159 (63.9%) critical patients. Compared to no corticosteroid use group, systemic corticosteroid use showed no benefit in reducing in-hospital mortality in both severe cases (HR=1.77, 95% CI: 1.08-2.89, p=0.023), and critical cases (HR=2.07, 95% CI: 1.08-3.98, p=0.028). In the time-varying Cox analysis that with time varying exposure, systemic corticosteroid use still showed no benefit in either population (for severe patients, HR=2.83, 95% CI: 1.72-4.64, p< 0.001; for critical patients, HR=3.02, 95% CI: 1.59-5.73, p=0.001). Baseline characteristics were matched after IPTW and PSM analysis. For severe COVID-19 patients at admission, corticosteroid use was not associated with improved outcome in either the IPTW analysis. For critical COVID-19 patients at admission, results were consistent with former analysis that corticosteroid use did not reduce in-hospital mortality. Conclusions: Corticosteroid use showed no benefit in reducing in-hospital mortality for severe or critical cases. The routine use of systemic corticosteroids among severe and critical COVID-19 patients was not recommended.


title: Single cell resolution landscape of equine peripheral blood mononuclear cells reveals diverse immune cell subtypes including T-bet+ B cells

text: Traditional laboratory model organisms represent a small fraction of the diversity of multicellular life, and findings in any given experimental model often do not translate to other species. Immunology research in non-traditional model organisms can be advantageous or even necessary (e.g. for host-pathogen interaction studies), but presents multiple challenges, many stemming from an incomplete understanding of potentially species-specific immune cell types, frequencies and phenotypes. Identifying and characterizing immune cells in such organisms is frequently limited by the availability of species-reactive immunophenotyping reagents for flow cytometry, and insufficient prior knowledge of cell type-defining markers. Here, we demonstrate the utility of single cell RNA sequencing (scRNA-Seq) to characterize immune cells for which traditional experimental tools are limited. Specifically, we used scRNA-Seq to comprehensively define the cellular diversity of equine peripheral blood mononuclear cells (PBMCs) from healthy horses across different breeds, ages, and sexes. We identified 30 cell type clusters partitioned into five major populations: Monocytes/Dendritic Cells, B cells, CD3+PRF1+ lymphocytes, CD3+PRF1- lymphocytes, and Basophils. Comparative analyses revealed many cell populations analogous to human PBMC, including transcriptionally heterogeneous monocytes and distinct dendritic cell subsets (cDC1, cDC2, plasmacytoid DC). Unexpectedly, we found that a majority of the equine peripheral B cell compartment is comprised of T-bet+ B cells; an immune cell subpopulation typically associated with chronic infection and inflammation in human and mouse. Taken together, our results demonstrate the potential of scRNA-Seq for cellular analyses in non-traditional model organisms, and form the basis for an immune cell atlas of horse peripheral blood.


title: GHSR-1a is not Required for Ghrelin’s Anti-inflammatory and Fat-sparing Effects in Cancer Cachexia

text: Adipose tissue (AT) atrophy is a hallmark of cancer cachexia contributing to increased morbidity/mortality. Ghrelin has been proposed as a treatment for cancer cachexia partly by preventing AT atrophy. However, the mechanisms mediating ghrelin’s effects are incompletely understood, including the extent to which its only known receptor, GHSR-1a, is required for these effects. This study characterizes the pathways involved in AT atrophy in the Lewis Lung Carcinoma (LLC)-induced cachexia model and those mediating the effects of ghrelin in Ghsr+/+ and Ghsr−/− mice. We show that LLC causes AT atrophy by inducing anorexia, and increasing AT inflammation, thermogenesis and energy expenditure. These changes were greater in Ghsr−/−. Ghrelin administration prevented LLC-induced anorexia only in Ghsr+/+, but prevented WAT inflammation and atrophy in both genotypes, although its effects were greater in Ghsr+/+. LLC-induced increases in BAT inflammation, WAT and BAT thermogenesis, and energy expenditure were not affected by ghrelin. In conclusion, ghrelin ameliorates WAT inflammation, fat atrophy and anorexia in LLC-induced cachexia. GHSR-1a is required for ghrelin’s orexigenic effect but not for its anti-inflammatory or fat-sparing effects.


title: Factors associated with country-variation in COVID-19 morbidity and mortality worldwide: an observational geographic study

text: Background: The world is threatened by the outbreak of coronavirus disease 19 (COVID-19) since December 2019. The number of cases and deaths increased dramatically in some countries from March 2020. The objective of our study was to examine potential associated factors with country-variation in COVID-19 morbidity and mortality in the world. Methods: We performed a retrospective geographic study including all countries with the most recent available data on free access on the web. We analyzed univariate and multivariable correlation between both the number of reported cases and deaths by country and demographic, socioeconomic characteristics, lockdown as major control measure, average annual temperature and relative humidity. We performed simple linear regression, independent t test and ANOVA test for univariate analyses and negative binomial regression model for multivariable analyses. Results: We analyzed data of 186 countries from all world regions. As of 13th April 2020, a total of 1 804 302 COVID-19 cases and 113 444 deaths were reported. The reported number of COVID-19 cases and deaths by countries was associated with the number of days between the first case and lockdown, the number of cases at lockdown, life expectancy at birth, average annual temperature and the socio-economic level. Countries which never implemented BCG vaccination reported higher mortality than others. Conclusions: The pandemic is still ongoing and poses a global health threat as there is no effective antiviral treatment or vaccines. Thus, timing of control measure implementation is a crucial factor in determining the spread of the epidemic. It should be a lesson for this pandemic and for the future.


Unprecedented Times Call for Unprecedented Collaboration: How Two COVID-19 Surveys Were Created with Input from Across the Field of Visual Impairment to Analyze the Needs of Adults, Students, Teachers, and Orientation and Mobility Practitioners


title: Analysis of SARS-CoV-2-controlled autophagy reveals spermidine, MK-2206, and niclosamide as putative antiviral therapeutics

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses an acute threat to public health and the world economy, especially because no approved specific drugs or vaccines are available. Pharmacological modulation of metabolism-dependent cellular pathways such as autophagy reduced propagation of highly pathogenic Middle East respiratory syndrome (MERS)-CoV. Here we show that SARS-CoV-2 infection limits autophagy by interfering with multiple metabolic pathways and that compound-driven interventions aimed at autophagy induction reduce SARS-CoV-2 propagation in vitro. In-depth analyses of autophagy signaling and metabolomics indicate that SARS-CoV-2 reduces glycolysis and protein translation by limiting activation of AMP-protein activated kinase (AMPK) and mammalian target of rapamycin complex 1 (mTORC1). Infection also downregulates autophagy-inducing spermidine, and facilitates AKT1/SKP2-dependent degradation of autophagy-initiating Beclin-1 (BECN1). Targeting of these pathways by exogenous administration of spermidine, AKT inhibitor MK-2206, and the Beclin-1 stabilizing, antihelminthic drug niclosamide inhibited SARS-CoV-2 propagation by 85, 88, and >99%, respectively. In sum, SARS-CoV-2 infection causally diminishes autophagy. A clinically approved and well-tolerated autophagy-inducing compound shows potential for evaluation as a treatment against SARS-CoV-2.


title: Correlation between meteorological factors and COVID-19 infection in the Belem Metropolitan Region

text: Many factors can influence then spread of viruses and respiratory infections. Studies have suggested that there is a direct relationship between environmental issues and population density with cases of COVID-19. In this sense, this research aims to analyze, through correlational study and Krigagem, the relationship of meteorological and demographic variables with cases of COVID-19 in regions of subtropical climate in Brazil. The results suggest that population and demographic density (hab/km2) are risk factors for the spread of SAR-CoV-2 and an increase in the daily case record of COVID-19. The distribution of cases according to age group did not present a significant disparity between men and women. Relative humidity (RH)%, average temperature Celsius, minimum temperature Celsius, maximum temperature Celsius, wind speed m/s and daily precipitation (rain) mm show negative relationships with cases of COVID-19 in regions of humid equatorial climate. Analysis between associations of environmental factors, wind, temperature and HR in a region is extremely important to understand the dynamics of SARS-CoV-2 in the environment. In the northern region of Brazil, low wind speed, high temperatures and high RH are observed, environmental factors that, when associated, reduce the transmission process because it hinders the movement of the virus in the environment. In this sense, it is suggested that the transmission of SARS-CoV-2 in this region is disseminated through fluids in the air between man/man and by contact between objects/men. Therefore, strategic public policies to combat the pandemic must consider the environmental factors of the regions involved and control and/or blocking the transit of people.


Global Spread of Coronavirus: Preparing Health Care Workers


title: Mental health during the COVID-19 pandemic in two longitudinal UK population cohorts

text: Background: The impact of COVID-19 on mental health is unclear. Evidence from longitudinal studies with pre pandemic data are needed to address (1) how mental health has changed from pre-pandemic levels to during the COVID-19 pandemic and (2), whether there are groups at greater risk of poorer mental health during the pandemic? Methods: We used data from COVID-19 surveys (completed through April/May 2020), nested within two large longitudinal population cohorts with harmonised measures of mental health: two generations of the Avon Longitudinal Study of Parents and Children (ALPSAC): the index generation ALSPAC-G1 (n= 2850, mean age 28) and the parents generation ALSPAC-G0 (n= 3720, mean age = 59) and Generation Scotland: Scottish Family Health Study (GS, (n= 4233, mean age = 59), both with validated pre-pandemic measures of mental health and baseline factors. To answer question 1, we used ALSPAC-G1, which has identical mental health measures before and during the pandemic. Question 2 was addressed using both studies, using pre-pandemic and COVID-19 specific factors to explore associations with depression and anxiety in COVID-19. Findings: In ALSPAC-G1 there was evidence that anxiety and lower wellbeing, but not depression, had increased in COVID-19 from pre-pandemic assessments. The percentage of individuals with probable anxiety disorder was almost double during COVID-19: 24% (95% CI 23%, 26%) compared to pre-pandemic levels (13%, 95% CI 12%, 14%), with clinically relevant effect sizes. In both ALSPAC and GS, depression and anxiety were greater in younger populations, women, those with pre-existing mental and physical health conditions, those living alone and in socio-economic adversity. We did not detect evidence for elevated risk in key workers or health care workers. Interpretation: These results suggest increases in anxiety and lower wellbeing that may be related to the COVID-19 pandemic and/or its management, particularly in young people. This research highlights that specific groups may be disproportionally at risk of elevated levels of depression and anxiety during COVID-19 and supports recent calls for increasing funds for mental health services. Funding: The UK Medical Research Council (MRC), the Wellcome Trust and University of Bristol.


title: A 5-min RNA preparation method for COVID-19 detection with RT-qPCR

text: RNA extraction has become a bottleneck for detection of COVID-19, in part because of reagent shortages. We present here a rapid protocol that circumvents the need for RNA extraction that is compatible with RT-qPCR-based detection methods.


title: STAT2 signaling as double-edged sword restricting viral dissemination but driving severe pneumonia in SARS-CoV-2 infected hamsters

text: Since the emergence of SARS-CoV-2 causing COVID-19, the world is being shaken to its core with numerous hospitalizations and hundreds of thousands of deaths. In search for key targets of effective therapeutics, robust animal models mimicking COVID-19 in humans are urgently needed. Here, we show that productive SARS-CoV-2 infection in the lungs of mice is limited and restricted by early type I interferon responses. In contrast, we show that Syrian hamsters are highly permissive to SARS- CoV-2 and develop bronchopneumonia and a strong inflammatory response in the lungs with neutrophil infiltration and edema. Moreover, we identify an exuberant innate immune response as a key player in pathogenesis, in which STAT2 signaling plays a dual role, driving severe lung injury on the one hand, yet restricting systemic virus dissemination on the other. Finally, we assess SARS-CoV- 2-induced lung pathology in hamsters by micro-CT alike used in clinical practice. Our results reveal the importance of STAT2-dependent interferon responses in the pathogenesis and virus control during SARS-CoV-2 infection and may help rationalizing new strategies for the treatment of COVID-19 patients.


title: Can Search Query Forecast successfully in China's 2019-nCov pneumonia?

text: Recently the novel coronavirus (2019-nCov) pneumonia outbreak in China then the world, and the Number of infections and death continues to increases. Search Query performs well in forecasting the epidemics. It is still a question whether search engine data can forecast the drift and the inflexion in 2019-nCov pneumonia. Based on the Baidu Search Index, we propose three prediction models: composite Index, composite Index with filtering and suspected NCP(Novel Coronavirus Pneumonia). The result demonstrates that the predictive model of composite index with filtering performs the best while the model of suspected NCP has the highest forecast error. We further predict the out-of-the-set NCP confirmed cases and monitor that the next peak of new diagnoses will occur on February 16th and 17th.


title: COVID-19 scenarios for the United States

text: The United States (US) has not been spared in the ongoing pandemic of novel coronavirus disease. COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), continues to cause death and disease in all 50 states, as well as significant economic damage wrought by the non-pharmaceutical interventions (NPI) adopted in attempts to control transmission. We use a deterministic, Susceptible, Exposed, Infectious, Recovered (SEIR) compartmental framework to model possible trajectories of SARS-CoV-2 infections and the impact of NPI at the state level. Model performance was tested against reported deaths from 01 February to 04 July 2020. Using this SEIR model and projections of critical driving covariates (pneumonia seasonality, mobility, testing rates, and mask use per capita), we assessed some possible futures of the COVID-19 pandemic from 05 July through 31 December 2020. We explored future scenarios that included feasible assumptions about NPIs including social distancing mandates (SDMs) and levels of mask use. The range of infection, death, and hospital demand outcomes revealed by these scenarios show that action taken during the summer of 2020 will have profound public health impacts through to the year end. Encouragingly, we find that an emphasis on universal mask use may be sufficient to ameliorate the worst effects of epidemic resurgences in many states. Masks may save as many as 102,795 (55,898-183,374) lives, when compared to a plausible reference scenario in December. In addition, widespread mask use may markedly reduce the need for more socially and economically deleterious SDMs.


title: Accessibility and allocation of public parks and gardens during COVID-19 social distancing in England and Wales

text: Visiting parks and gardens may attenuate the adverse physical and mental health impacts of social distancing implemented to reduce the spread of COVID-19. We quantified access to public parks and gardens in urban areas of England and Wales, and the potential for park crowdedness during periods of high use. We combined data from the Office for National Statistics and Ordnance Survey to quantified (i) the number of parks within 500 and 1,000 metres of urban postcodes (i.e., availability), (ii) the distance of postcodes to the nearest park (i.e., accessibility), and (iii) per-capita space in each park for people living within 1,000m. We examined variability by city and share of flats. Around 25.4 million people can access public parks or gardens within a ten-minute walk, while 3.8 million residents live farther away; of these 21% are children and 13% are elderly. Areas with a higher share of flats on average are closer to a park but people living in these areas are potentially less able to meet social distancing requirements while in parks during periods of high use. Cities in England and Wales can provide residents with access to green space that enables outdoor exercise and play during social distancing. Keeping public parks and gardens open, might require measures such as dedicated park times for different age groups or entry allocation systems that, combined with smartphone apps or drones, can monitor and manage the total number of people using the park.


title: Automatic X-ray COVID-19 Lung Image Classification System based on Multi-Level Thresholding and Support Vector Machine

text: Abstract- The early detection of SARS-CoV-2, the causative agent of (COVID-19) is now a critical task for the clinical practitioners. The COVID-19 spread is announced as pandemic outbreak between people worldwide by WHO since 11/ March/ 2020. In this consequence, it is top critical priority to become aware of the infected people so that prevention procedures can be processed to minimize the COVID-19 spread and to begin early medical health care of those infected persons. In this paper, the deep studying based totally methodology is usually recommended for the detection of COVID-19 infected patients using X-ray images. The help vector gadget classifies the corona affected X-ray images from others through usage of the deep features. The technique is useful for the clinical practitioners for early detection of COVID-19 infected patients. The suggested system of multi-level thresholding plus SVM presented high accuracy in classification of the infected lung with Covid-19. All images were of the same size and stored in JPEG format with 512 * 512 pixels. The average sensitivity, specificity, and accuracy of the lung classification using the proposed model results were 95.76%, 99.7%, and 97.48%, respectively.


Prevention and Control of COVID-19


title: The Population Attributable Fraction (PAF) of cases due to gatherings and groups with relevance to COVID-19 mitigation strategies

text: Background Many countries have banned groups and gatherings as part of their response to the pandemic caused by the coronavirus, SARS-CoV-2. Although there are outbreak reports involving mass gatherings, the contribution to overall transmission is unknown. Methods We used data from a survey of social contact behaviour that specifically asked about contact with groups to estimate the Population Attributable Fraction (PAF) due to groups as the relative change in the Basic Reproduction Number when groups are prevented. Findings We estimate that PAF due to groups of 50+ people is 2.2% (95%CI 1.1%, 3.6%); the PAF due to groups of 20+ people is 6.4% (5.0%, 8.0%); the PAF due to groups of 10+ is 11.3% (9.9%, 13.0%) Interpretation Large groups of individuals have a small epidemiological impact; small and medium sized groups between 10 and 50 people have a larger impact on an epidemic.


title: Chest CT Images for COVID-19: Radiologists and Computer-based detection

text: Background Characteristic chest computed tomography (CT) manifestation of 2019 novel coronavirus (COVID-19) was added as a diagnostic criterion in the Chinese National COVID-19 management guideline. Whether the characteristic findings of Chest CT could differentiate confirmed COVID-19 cases from other positive nucleic acid test (NAT)-negative patients has not been rigorously evaluated. Purpose We aim to test whether chest computed tomography (CT) manifestation of 2019 novel coronavirus (COVID-19) can be differentiated by a radiologist or a computer-based CT image analysis system. Methods We conducted a retrospective case-control study that included 52 laboratory-confirmed COVID-19 patients and 80 non-COVID-19 viral pneumonia patients between 20 December, 2019 and 10 February, 2020. The chest CT images were evaluated by radiologists in a double blind fashion. A computer-based image analysis system (uAI system, Lianying Inc., Shanghai, China) detected the lesions in 18 lung segments defined by Boyden classification system and calculated the infected volume in each segment. The number and volume of lesions detected by radiologist and computer system was compared with Chi-square test or Mann-Whitney U test as appropriate. Results The main CT manifestations of COVID-19 were multi-lobar/segmental peripheral ground-glass opacities and patchy air space infiltrates. The case and control groups were similar in demographics, comorbidity, and clinical manifestations. There was no significant difference in eight radiologist identified CT image features between the two groups of patients. There was also no difference in the absolute and relative volume of infected regions in each lung segment. Conclusions We documented the non-differentiating nature of initial chest CT image between COVID-19 and other viral pneumonia with suspected symptoms. Our results do not support CT findings replacing microbiological diagnosis as a critical criterion for COVID-19 diagnosis. Our findings may prompt re-evaluation of isolated patients without laboratory confirmation.


title: Prognostic value of C-reactive protein in patients with COVID-19

text: Background Elevated serum C-reactive protein (CRP) level was observed in most patients with COVID-19. Methods Data of COVID-19 patients with clinical outcome in a designated hospital in Wuhan, China, were retrospectively collected and analyzed from Jan 30 to Feb 20, 2020. The prognostic value of admission CRP was evaluated in patients with COVID-19. Results Out of 298 patients enrolled, 84 died and 214 recovered. Most non-survivors tended to be males, old aged, or with chronic diseases. Compared to survivors, non-survivors showed significantly higher white blood cell and neutrophil count, neutrophil to lymphocyte ratio (NLR), systemic immune-inflammation index (SII, defined by platelet count multiply by NLR), CRP, procalcitonin, and D-dimer, and lower red blood cell, lymphocyte, and platelet count. Age, neutrophil count, platelet count, and CRP were identified as independent predictors of adverse outcome. The area under the receiver operating characteristic (ROC) curve (AUC) of CRP (0.896) was significantly higher than that of age (0.833), neutrophil count (0.820), and platelet count (0.678) in outcome prediction (all p<0.05). With a cut-off value of 41.4, CRP exhibited sensitivity 90.5%, specificity 77.6%, positive predictive value 61.3%, and negative predictive value 95.4%. Subgroup analysis revealed that CRP remained robust accuracy in adverse outcome prediction in patients with different disease severity (AUC 0.832, z=10.23, p<0.001; AUC 0.989, z=44.04, p<0.001). CRP was also an independent discriminator of severe/critical illness on admission (AUC 0.783, z=10.69, p<0.001). Conclusions In patients with COVID-19, admission CRP correlated with disease severity and tended to be a good predictor of adverse outcome.


title: The COVID-19 pandemic and the implementation of telehealth in speech-language and hearing therapy for patients at home: an experience report

text: We present an experience report on the implementation of real-time telehealth in speech-language and hearing therapy for patients who were previously seen on an outpatient basis in a primary health care service The Speech-Language Therapy (SLT) team was monitoring twenty-five users when the first cases of COVID-19 were notified in southern Brazil Of these, it was judged that twelve patients required at least a monitoring call every two weeks Teleconsultations were available in this first stage, on an emergency basis, during the implementation of the project in this format The idea was to guarantee, due to the suspension of the SLT sessions, the maintenance of the care service for patients who could suffer worsening of their cases or even comorbidities The appointments were carried out by video calls by SLT students, therapists of the extension project, and supervised by a speech-language therapist, synchronously All conversations and orientations during the teleconsultation were conducted as calmly as possible and, in the case of infant patients, permeated by some playful activities Telehealth has shown to be an efficient resource for the care of patients with SLT demands, enabling remote care with the same quality as face-to-face care Besides, it has relevant potential, once there is a significant number of patients, who need SLT assessment and live in regions where there is a shortage of qualified professionals


title: Detection of SARS-CoV-2 in Exhaled Breath from COVID-19 Patients Ready for Hospital Discharge

text: The COVID-19 pandemic has brought an unprecedented crisis to the global health sector1. When recovering COVID-19 patients are discharged in accordance with throat or nasal swab protocols using reverse transcription polymerase chain reaction (RT-PCR), the potential risk of re-introducing the infection source to humans and the environment must be resolved 2,3,4. Here we show that 20% of COVID-19 patients, who were ready for a hospital discharge based on current guidelines, had SARS-CoV-2 in their exhaled breath (~105 RNA copies/m3). They were estimated to emit about 1400 RNA copies into the air per minute. Although fewer surface swabs (1.3%, N=318) tested positive, medical equipment frequently contacted by healthcare workers and the work shift floor were contaminated by SARS-CoV-2 in four hospitals in Wuhan. All air samples (N=44) appeared negative likely due to the dilution or inactivation through natural ventilation (1.6-3.3 m/s) and applied disinfection. Despite the low risk of cross environmental contamination in the studied hospitals, there is a critical need for strengthening the hospital discharge standards in preventing re-emergence of COVID-19 spread.


Evidence-Based Medicine: What Neurologists Need to Remember During the COVID-19 Pandemic


title: Modeling the Worldwide Spread of Pandemic Influenza: Baseline Case and Containment Interventions

text: We present a study of the worldwide spread of a pandemic influenza and its possible containment at a global level taking into account all available information on air travel. We studied a metapopulation stochastic epidemic model on a global scale that considers airline travel flow data among urban areas. We provided a temporal and spatial evolution of the pandemic with a sensitivity analysis of different levels of infectiousness of the virus and initial outbreak conditions (both geographical and seasonal). For each spreading scenario we provided the timeline and the geographical impact of the pandemic in 3,100 urban areas, located in 220 different countries. We compared the baseline cases with different containment strategies, including travel restrictions and the therapeutic use of antiviral (AV) drugs. We show that the inclusion of air transportation is crucial in the assessment of the occurrence probability of global outbreaks. The large-scale therapeutic usage of AV drugs in all hit countries would be able to mitigate a pandemic effect with a reproductive rate as high as 1.9 during the first year; with AV supply use sufficient to treat approximately 2% to 6% of the population, in conjunction with efficient case detection and timely drug distribution. For highly contagious viruses (i.e., a reproductive rate as high as 2.3), even the unrealistic use of supplies corresponding to the treatment of approximately 20% of the population leaves 30%-50% of the population infected. In the case of limited AV supplies and pandemics with a reproductive rate as high as 1.9, we demonstrate that the more cooperative the strategy, the more effective are the containment results in all regions of the world, including those countries that made part of their resources available for global use.


title: Room-temperature-storable PCR Mixes for SARS-CoV-2 Detection

text: A novel coronavirus (severe acute respiratory syndrome coronavirus 2, SARS-CoV-2) emerged in late 2019, causing an outbreak of pneumonia [coronavirus disease 2019 (COVID-19)] in Wuhan, China, which then rapidly spread globally. Although the use of ready-made reaction mixes can enable more rapid PCR-based diagnosis of COVID-19, the need to transport and store these mixes at low temperatures presents challenges to already overburdened logistics networks. Here, we present an optimized freeze-drying procedure that allows SARS-CoV-2 PCR mixes to be transported and stored at ambient temperatures, without loss of activity. Additive-supplemented PCR mixes were freeze-dried. The residual moisture of the freeze-dried PCR mixes was measured by Karl-Fischer titration. We found that freeze-dried PCR mixes with ∼1.2% residual moisture are optimal for storage, transport, and reconstitution. The sensitivity, specificity, and repeatability of the freeze-dried reagents were similar to those of freshly prepared, wet reagents. The freeze-dried mixes retained activity at room temperature (18∼25°C) for 28 days, and for 14 and 10 days when stored at 37°C and 56°C, respectively. The uptake of this approach will ease logistical challenges faced by transport networks and make more cold storage space available at diagnosis and hospital laboratories. This method can also be applied to the generation of freeze-dried PCR mixes for the detection of other pathogens.


title: COVID-19 diagnosis prediction in emergency care patients: a machine learning approach

text: The coronavirus disease (COVID-19) pandemic has increased the necessity of immediate clinical decisions and effective usage of healthcare resources. Currently, the most validated diagnosis test for COVID-19 (RT-PCR) is in shortage in most developing countries, which may increase infection rates and delay important preventive measures. The objective of this study was to predict the risk of positive COVID-19 diagnosis with machine learning, using as predictors only results from emergency care admission exams. We collected data from a sample of 235 adult patients from the Hospital Israelita Albert Einstein in Sao Paulo, Brazil, from 17 to 30 of March, 2020, of which 102 (43%) received a positive diagnosis of COVID-19 from RT-PCR tests. Five machine learning algorithms (neural networks, random forests, gradient boosting trees, logistic regression and support vector machines) were trained on a random sample of 70% of the patients, and performance was tested on new unseen data (30%). The best predictive performance was obtained by the support vector machines algorithm (AUC: 0.85; Sensitivity: 0.68; Specificity: 0.85; Brier Score: 0.16). In conclusion, we found that targeted decisions for receiving COVID-19 tests using only routinely-collected data is a promising new area with the use of machine learning algorithms.


title: COVID-19 Progression Timeline and Effectiveness of Response-to-Spread Interventions across the United States

text: Motivated by the rapid upsurge of COVID-19 cases in the United States beginning March 2020, we forecast the disease spread and assess the effectiveness of containment strategies by using an estalished network-driven epidemic dynamic model. Our model is initialized using the daily counts of active and confirmed COVID-19 cases across the US. Based on our model predictions for the March 14-16 timeframe, the national epidemic peak could be expected to arrive by early June, corresponding to a daily active count of ≈ 7% of the US population, if no containment plans are implemented. Epidemic peaks are expected to arrive in the states of Washington and New York by May 21 and 25, respectively. With a modest 25% reduction in COVID-19 transmissibility via community-level interventions, the epidemic progression could be delayed by up to 34 days. Wholesale interstate traffic restriction is ineffective in delaying the epidemic outbreak, but it does desynchronize the arrival of state-wise epidemic peaks, which could potentially alleviate the burden on limited available medical resources. In addition to forecasting the arrival timeline of the state-wise epidemic peaks, we attempt at informing the optimal timing necessary to enforce community-level interventions. Our findings underscore the pressing need for preparedness and timely interventions in states with a large fraction of the vulnerable uninsured and liquid-asset-poverty populations.


title: Cerebral Venous Thrombosis: Atypical Presentation of COVID-19 in the Young

text: Abstract Objective Identify clinical and radiographic features of venous infarct as a presenting feature of COVID-19 in the young. Background SARS-CoV-2 infection causes hypercoagulability and inflammation leading to venous thrombotic events (VTE). Although elderly patients with comorbidities are at higher risk, COVID-19 may also cause VTE in a broader patient population without these risks. Neurologic complications and manifestations of COVID-19, including neuropathies, seizures, strokes and encephalopathy usually occur in severe established cases of COVID-19 infection who primarily present with respiratory distress. Case description : Case report of a 29-year-old woman, with no significant past medical history or comorbidities, presenting with new onset seizures. Further questioning revealed a one-week history of headaches, low-grade fever, mild cough and shortness of breath, diagnosed as COVID-19. Imaging revealed a left temporoparietal hemorrhagic venous infarction with left transverse and sigmoid sinus thrombosis treated with full dose anticoagulation and antiepileptics. Conclusion Although elderly patients with comorbidities are considered highest risk for COVID-19 neurologic complications, usually when systemic symptoms are severe, this case report emphasizes that young individuals are at risk for VTE with neurologic complications even when systemic symptoms are mild, likely induced by COVID-19 associated hypercoagulable state.


title: COVID-19 in Patients with Solid Organ Transplantation: A Systematic Review

text: The novel coronavirus, SARS-CoV-2, is causing a pandemic of unknown precedent, with huge healthcare challenges and worldwide disruptions to economic and social life Lung transplant recipients and other solid organ transplant (SOT) recipients are immunosuppressed, and therefore are generally considered at an increased risk for severe infections Given the current gap in knowledge and evidence regarding the best management of these patients, we conducted a systematic review of studies on SARS-CoV-2 infections and Coronavirus Disease 2019 (COVID-19) in SOT recipients, to evaluate the association between immunosuppression in these patients, SARS-CoV-2 infection and COVID-19 outcomes The focus was the severity of the disease, the need for mechanical ventilation and intensive care unit (ICU) admissions, and rate of death The literature search was conducted repeatedly between 16 March and 8 April 2020 We searched original papers, observational studies, case reports, and meta-analyses published between 2019 and 2020 using two databases (PubMed, Google Scholar) with the search terms: [transplant OR immunosuppression] AND [COVID-19 OR SARS-CoV-2] Further inclusion criteria were publications in English, French, German and Italian, and reference to humans We also searched the reference lists of the studies encountered From an initial search of PubMed and Google Scholar, 19 potential articles were retrieved, of which 14 were excluded after full-text screening (not being case reports or case series), leaving 5 studies for inclusion No further studies were identified from the bibliographies of retrieved articles Based on the limited research, no firm conclusions can be made concerning SOT recipients, but the current evidence suggests that immunosuppression is most likely associated with a better outcome of SARS-CoV-2 infection and COVID-19 because it prevents hyperinflammation (cytokine storm) in this particular population There is a need for further research that would allow results to be adjusted for other factors potentially impacting COVID-19 severity and outcome


title: Population modeling of early COVID-19 epidemic dynamics in French regions and estimation of the lockdown impact on infection rate

text: We propose a population approach to model the beginning of the French COVID-19 epidemic at the regional level. We rely on an extended Susceptible-Exposed-Infectious-Recovered (SEIR) mechanistic model, a simplified representation of the average epidemic process. Combining several French public datasets on the early dynamics of the epidemic, we estimate region-specific key parameters conditionally on this mechanistic model through Stochastic Approximation Expectation Maximization (SAEM) optimization using Monolix software. We thus estimate basic reproductive numbers by region before isolation (between 2.4 and 3.1), the percentage of infected people over time (between 2.0 and 5.9% as of May 11th, 2020) and the impact of nationwide household confinement on the infection rate (decreasing the transmission rate by 72% toward a Re ranging from 0.7 to 0.9). We conclude that a lifting of the lockdown should be accompanied by further interventions to avoid an epidemic rebound.


title: COVID-19 trend in Bangladesh: deviation from epidemiological model and critical analysis of the possible factors

text: Background: Since its first report on March 08, COVID-19 positive cases and number of deaths are increasing in Bangladesh. In the first month of COVID-19 infection, incidence of daily positive cases did follow the susceptible, infected and recovered (SIR) based predictions we reported in April, but started to deviate in the following month. COVID-19 transmission and disease progression depends on multifaceted determinants e.g. viral genetics, host immunity, social distancing, co-morbidity, socio-demographic and environmental parameters. Therefore deviation in confirmed cases from predicted model may appear and warrant thorough investigation. In this short report, we tried to demonstrate and analyze the possible factors associated with the deviation which included preventive intervention strategies, socioeconomic capabilities, climatic and meteorological indexes, acquired immunity of Bangladeshi population, demographic characteristics, health indicators and food habits. Findings: The key factor responsible for the deviation was found to be the number of tests performed. Having population with low median age, young age groups are being mostly infected. Low prevalence of non-communicable diseases among them and strong immunity compared to the elderly might have kept most of them asymptomatic with silent recovery. Warm temperature, humidity and UV index of Bangladesh during this summer period might have contributed to the slow progression of infection. Longer daylight mediated immunity, fresh air circulations and ventilation, less density in rural areas and certain food habits perhaps helped the large number of populations to restrict the infection. Conclusion: Despite all these helpful determinants in Bangladesh, person to person contact is still the leading risk factor for COVID-19 transmission. Infection may increase rapidly if safe distance and preventive measures are not strictly followed while resuming the normal social and work life. A global second wave may hit in many countries in autumn and as well as in Bangladesh in mid-October when winter starts to approach. Strong collaborative action plans, strategies and implementation are needed immediately to prevent catastrophe.


title: Merck KGaA helps scale COVID-19 vaccine

text: The University of Oxford’s Jenner Institute and Merck KGaA have developed a manufacturing process for the institute’s COVID-19 vaccine candidate, ChAdOx1 nCoV-19 Using technology developed by Merck, the partners have reduced the process development phase from 12 months to 2 A trial of the vaccine, which is based on an adenovirus vaccine vector and the SARS-Cov-2 spike protein, will start soon and the vaccine could be ready to roll out by the fall, Jenner says


title: Silent Disease and Loss of Taste and Smell are Common Manifestations of SARS-COV-2 Infection in a Quarantine Facility: First report from Saudi Arabia

text: Abstract BACKGROUND The Coronavirus disease 2019 (COVID-19) outbreak in Saudi Arabia was first identified in a traveler from Al Qatif city, on March 2nd, 2020. The disease has quickly spread and reached multiple cities within a few weeks. In an attempt to limit the spread of COVID-19 in Saudi Arabia, the government has implemented strict regulations. Starting March 15th, all travelers coming back to the kingdom were tested for COVID-19 and were quarantined in a government-designated facility. The same rule was applied to all positive cases identified by contact tracing. In this study, we aimed to assess the prevalence of asymptomatic carriers, epidemiological characteristics, clinical presentations, and viral clearance of SARS-COV-2 positive quarantined individuals in a quarantine facility in the eastern province. METHODS We conducted a cross-sectional study on 128 laboratory-confirmed COVID-19 subjects who were quarantined in a government-designated facility. The study period was from March 16th until April 18th, 2020. We collected data on demographics and on clinical symptoms. Also, samples for PCR tests were collected upon admission and were repeated every 72 hours if they were still positive. All negative samples were repeated within 24 hours for confirmation. RESULTS Sixty-nine of the 128 residents (54%) were completely asymptomatic until the end of the study. The remaining 59 residents (46%) had only mild symptoms. The most common symptom was a sudden loss of smell and taste, accounting for 47.5%. The median time to virus clearance was significantly different between the two groups. Symptomatic residents cleared the virus at a median of 17 days (95% CI,12.4-21.6) from the first positive PCR vs. 11days (95% CI, 8.7-13.3) in the asymptomatic group (P=0.011). False-negative test results occurred in 18.8% of the total residents and false-positive results in 3%. CONCLUSION The prevalence of asymptomatic carriers is high in our study. Testing, and isolating travelers and contacts of laboratory-confirmed cases, regardless of symptoms, were very effective measures for early disease identification and containment. Loss of taste and smell was the most common presentation in our mild symptomatic residents, and it might be predictive of mild disease. The persistent positive PCRs observed in the mild asymptomatic residents despite being symptoms free, warrant further studies to determine its implications on disease spread and control.


title: Predicting COVID-19 spread and public health needs to contain the pandemic in West-Africa

text: The novel coronavirus (COVID-19) pandemic is causing devastating demographic, social, and economic damage globally. Understanding current patterns of the pandemic spread and forecasting its long-term trajectory is essential in guiding policies aimed at curtailing the pandemic. This is particularly important in regions with weak economies and fragile health care systems such as West-Africa. We formulate and use a deterministic compartmental model to (i) assess the current patterns of COVID-19 spread in West-Africa, (ii) evaluate the impact of currently implemented control measures, and (iii) predict the future course of the pandemic with and without currently implemented and additional control measures in West-Africa. An analytical expression for the threshold level of control measures (involving a reduction in the effective contact rate) required to eliminate the pandemic is computed. Considering currently applied health control measures, numerical simulations of the model using baseline parameter values estimated from West-African COVID-19 data project a 60% reduction in the daily number of cases when the epidemic attains its peak. More reduction in the number of cases will be achieved if additional public health control measures that result in a reduction in the effective contact rate are implemented. We found out that disease elimination is difficult when more asymptomatic individuals contribute in transmission or are not identified and isolated in a timely manner. However, maintaining a baseline level of asymptomatic isolation and a low transmission rate will lead to a significant reduction in the number of daily cases when the pandemic peaks. For example, at the baseline level of asymptomatic isolation, at least a 53% reduction in the transmission rate is required for disease elimination, while disease elimination is also possible if asymptomatic individuals are identified and isolated within 2 days (after the incubation period). Combining two or more measures is better for disease control, e.g., if asymptomatic humans are contact traced or identified and isolated in less than 3 days then only about a 31% reduction in the disease transmission rate is required for disease elimination. Furthermore, we showed that the currently implemented measures caused the time-dependent effective reproduction number to reduce by approximately 37% from February 28, to August 24, 2020. We conclude that COVID-19 elimination requires more control measures than what is currently being applied inWest-Africa and that mass testing and contact tracing in order to identify and isolate asymptomatic individuals early is very important in curtailing the burden of the pandemic.


title: Appendix 2 Acronyms

text: Unknown


title: COVID-19 and children with cancer: Parents' experiences, anxieties, and support needs

text: Background Children with cancer were considered to be extremely clinically vulnerable to severe COVID-19 disease if they were to contract SARS-CoV-2 due to immune suppression as a result of anti-cancer treatment. The aim was to explore experiences, information and support needs, and decision-making of parents with a child with cancer in response to the early phase of the COVID-19 pandemic in the UK. Methods Parents of a child with cancer completed a survey in April 2020, as the UK moved into a period of "lockdown", with restrictions of movement outside of the home. An online survey was developed to capture parents' experiences, information and support needs, and decision-making, using closed statements and open text boxes. Descriptive quantitative analyses and qualitative thematic content analysis were undertaken. Findings 171 parents/caregivers completed the survey. 85% of parents worried about the virus and the majority of parents were vigilant about virus (92%) or cancer symptoms (93.4%). For two-thirds (69.6%) hospital was no longer considered a safe place. Parents worried about their own health (81.1%) and about the child getting the virus from them (89.1%). Eight overarching themes, related to the virus: 1) risk of infection, 2) information, guidance and advice, 3) health care provision, 4) fears and anxieties; or related to lockdown/isolation: 5) psychological and social impact, 6) keeping safe under lockdown, 7) provisions and dependence, and 8) employment and income. Interpretation This is the first study to report experiences of parents of a child with cancer during the SARS-CoV-2/COVID-19 pandemic. The study demonstrated that the majority of parents are worried about SARS-CoV-2, and worried about transmitting the virus to their child. Hospital was no longer a safe place, and parents were worried about suboptimal cancer care. Parents describe fear and anxiety and the psychological, social and economic impact of isolation as a family.


title: Genetic Material and Sequence Data to Protect Global Health in the Light of Pandemic Outbreaks: Mapping the Legal Landscape under European and International Law

text: The current pandemic outbreak of corona virus SARS-CoV-2 shows the need for comprehensive European cooperation in drug development and the importance of genetic material and sequence data in research concerning this unknown disease As corona virus SARS-CoV-2 is spreading across Europe and worldwide, national authorities and the European Union (EU) institutions do their utmost to address the pandemic and accelerate innovation to protect global health In order to be prepared and to be able to respond immediately to serious epidemic and pandemic diseases, the EU has already adopted the Decision No (EU) 1082/2013 on serious cross-border threats to health The World Health Organization (WHO) has established a global system to collect genetic material and information to protect a global influenza pandemic outbreak The article describes the current legal landscape under EU and international law


title: SARS-CoV-2 infection induces germinal center responses with robust stimulation of CD4 T follicular helper cells in rhesus macaques

text: CD4 T follicular helper (Tfh) cells are important for the generation of long-lasting and specific humoral protection against viral infections. The degree to which SARS-CoV-2 infection generates Tfh cells and stimulates the germinal center response is an important question as we investigate vaccine options for the current pandemic. Here we report that, following infection with SARS-CoV-2, adult rhesus macaques exhibited transient accumulation of activated, proliferating Tfh cells in their peripheral blood on a transitory basis. The CD4 helper cell responses were skewed predominantly toward a Th1 response in blood, lung, and lymph nodes, reflective of the interferon-rich cytokine environment following infection. We also observed the generation of germinal center Tfh cells specific for the SARS-CoV-2 spike (S) and nucleocapsid (N) proteins, and a corresponding early appearance of antiviral serum IgG antibodies but delayed or absent IgA antibodies. Our data suggest that a vaccine promoting Th1-type Tfh responses that target the S protein may lead to protective immunity.


title: Structure of novel coronavirus’s spike protein solved

text: n a piece of research accomplished with astonishing speed, scientists from the University of Texas at Austin and the National Institutes of Health have released a cryo-electron microscopy (cryo-EM) structure of part of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus that has infected tens of thousands of people and killed more than 2,000 since the end of December (Science 2020, DOI: 10 1126/science abb2507) The part of the virus imaged, called the spike protein, helps the virus attach to and infect human cells, and the determination of its structure comes just weeks after the virus’s genome sequence was published The breakthrough is a huge step toward developing a vaccine against the virus as well as treatments for COVID-19, the disease that it causes, the researchers say UT Austin’s Jason McLellan and his colleagues, who have spent many years studying other coronaviruses, had already figured out how to use select


title: Estimation of COVID-19 dynamics in the different states of the United States using Time-Series Clustering

text: Estimation of COVID-19 dynamics and its evolution is a multidisciplinary effort, which requires the unification of heterogeneous disciplines (scientific, mathematics, epidemiological, biological/bio-chemical, virologists and health disciplines to mention the most relevant) to work together in a better understanding of this pandemic. Time series analysis is of great importance to determine both the similarity in the behavior of COVID-19 in certain countries/states and the establishment of models that can analyze and predict the transmission process of this infectious disease. In this contribution, an analysis of the different states of the United States will be carried out to measure the similarity of COVID-19 time series, using dynamic time warping distance (DTW) as a distance metric. A parametric methodology is proposed to jointly analyze infected and deceased persons. This metric allows to compare time series that have a different time length, making it very appropriate for studying the United States, since the virus did not spread simultaneously in all the states/provinces. After a measure of the similarity between the time series of the states of United States was determined, a hierarchical cluster was created, which makes it possible to analyze the behavioral relationships of the pandemic between different states and to discover interesting patterns and correlations in the underlying data of COVID-19 in the United States. With the proposed methodology, nine different clusters were obtained, showing a different behavior in the eastern zone and western zone of the United States. Finally, to make a prediction of the evolution of COVID-19 in the states, Logistic, Gompertz and SIR model was computed. With these mathematical model it is possible to have a more precise knowledge of the evolution and forecast of the pandemic.


title: Distributions and risks of SARS-CoV-2 in hospital outdoor environment

text: The outbreak of coronavirus infectious disease-2019 (COVID-19) pneumonia since 2019 has rapidly spread throughout over 200 countries around the world. Till 14th May 2020, there are over 4 million confirmed cases and 300,000 deaths globally. To date, numerous studies focus on the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in indoor areas for its main transmission routes via human respiratory droplets and direct contact. It remains unclear about the distribution and transmission risks of SARS-CoV-2 in outdoor environment despite its threats to healthy people and communities. Here, we investigated the presence of SARS-CoV-2 virus in 73 specimens from outdoor environment of three hospitals in Wuhan. We found SARS-CoV-2 in soils (205-550 copies/g), wastewaters (255 to 1.9x104 copies/L) and aerosols (285-1130 copies/m3) in locations close to departments receiving COVID-19 patients or in wastewater treatment sectors, which revealed significant viral spill-over in hospital outdoor environment that was possibly via respiratory droplets from patients or airborne aerosols from wastewater containing SARS-CoV-2. In contrast, SARS-CoV-2 was not detected in other areas or on surfaces with regular disinfection. Soils eventually behave as viral receptors through deposition and potentially a secondary source spreading SARS-CoV-2 for a prolonged time. Our findings map the high-risk areas in hospital outdoor environment possessing spread risks of SARS-CoV-2, which require particular attention and complete sanitation for preventing SARS-CoV-2 outdoor transmission.


title: Spectral analysis of the daily evolution of deaths due to Covid-19 in France and in the world shows a weekend effect: myth or reality?

text: Background The weekend effect has been extensively observed for different diseases and countries and recognized as a fact but without obvious causes. Objectives In this paper we first aimed at investigating the existence of a periodicity in the death count due to Covid-19, and second, at opening the discussion concerning the reality of this effect in this particular context. Methods Daily statistics of deaths due to the Covid-19 pandemic were subjected to a discrete Fourier transform spectral analysis for France and the world, over the periods from March 29 to May 16, 2020 and from January 22 to May 18, 2020 respectively. Results In both cases, a frequency peak of one harmonic corresponding to a period of 7.11 days was observed for France and the world. In France, this weekly frequency corresponds to a decrease in deaths every Sunday, whereas for the world the systematic decrease is shifted on average by 1.5 days and corresponds to Saturday or Friday. Conclusion At the world scale and for the epidemic period we confirm the existence of a consecutive weekend effect in the context of the Covid-19 pandemic.


title: Study of the mental health status of medical personnel dealing with new coronavirus pneumonia

text: Objective: This paper studied the relationship between personality traits and mental health conditions of medical personnel to provide a basis and reference for the implementation of targeted education on mental health. Methods: A self-report inventory, the Symptom Checklist-90 (SCL-90), was used to investigate the mental health status of 548 medical personnel dealing with the new coronavirus pneumonia in eight provinces and cities of China. Results: The overall mean SCL-90 score and mean values of factors (somatization, obsessive-compulsive, anxiety, phobic anxiety, and psychoticism) of the medical personnel were significantly higher than in the norm group (p < 0.05), while their average interpersonal sensitivity score was significantly lower (p < 0.01). In addition, personal factors affecting the mental health status of medical personnel were identified. ( all p < 0.05). Conclusion: The overall mental health status of medical personnel responding to new coronavirus pneumonia is generally higher than that of the norm group in China. The results of this study should contribute to measures to alleviate the psychological pressures on medical personnel dealing with the new coronavirus epidemic in China


title: Evaluating the determinants of COVID-19 mortality: A cross-country study

text: As the COVID-19 pandemic has spread to the entire world, a race to understand the virus and to find an effective and safe vaccine or treatment has triggered interest in the factors contributing to mortality. For instance, some studies have suggested that the BCG vaccine could protect from COVID-19 and nicotine patches could be therapeutic against the virus. This study makes use of data for about 140 countries to evaluate the determinants of COVID-19 mortality. It finds that a country's share of spending on health care (as a measure of a country's effectiveness in tracking, recording, and reporting COVID-19 deaths) is positively associated with COVID-19 deaths. It also finds that the share of people above 65 years of age, obesity, and urbanization are all positively associated with COVID-19 mortality. There is no evidence that BCG vaccination, smoking prevalence, and PM25 pollution have any link to COVID-19 mortality. These estimation results are robust to alternative specifications and after controlling for confounding factors and excluding outliers. Policymakers should allocate resources towards the protection of the elderly and those suffering from underlying conditions such as obesity. They should also exercise caution about administering nicotine patches or the BCG vaccine to fight COVID-19 without the backing of concrete scientific evidence.


title: Prediction on Covid-19 epidemic for different countries: Focusing on South Asia under various precautionary measures

text: The coronavirus disease 2019 (COVID-19), which emerged from Wuhan, China, is now a pandemic, affecting across the globe. Government of different countries have developed and adopted various policies to contain this epidemic and the most common were the social distancing and lockdown. We proposed a SEIR epidemic model that accommodates the effects of lockdown and individual based precautionary measures and used it to estimate model parameters from the epidemic data up to 2nd April, 2020, freely available in GitHub repository for COVID-19, for nine developed and developing countries. We used the estimated parameters to predict the disease burden in these countries with special emphasis on India, Bangladesh and Pakistan. Our analysis revealed that the lockdown and recommended individual hygiene can slow down the outbreak but unable to eradicate the disease from the society. With the current human-to-human transmission rate and existing level of personal precautionary, the number of infected individuals in India will be increasing at least for the next 3 months and the peak will come in 5 months. We can, however, reduce the epidemic size and prolong the time to arrive epidemic peak by seriously following the measures suggested by the authorities. We need to wait for another one month to obtain more data and epidemiological parameters for giving a better prediction about the pandemic. It is to be mentioned that research community is working for drugs and/ or vaccines against COVID19 and the presence of such pharmaceutical interventions will significantly alter the results.


title: Performance of suspected influenza case definitionbefore and during the COVID-19 pandemic

text: Background: The influenza-related burden remains high and the COVID-19 pandemic may difficult its accurate surveillance. This study aimed to evaluate the performance, before and during the COVID-19 pandemic, of the case definition of suspected influenza used in community surveillance in Mexico. Methods: A cross-sectional analysis of a cohort study took place and cases fulfilling the suspected case criteria (n = 20,511), and with laboratory-conclusive evidence (quantitative real-time polymerase chain reaction) to confirm or discard influenza virus infection were analyzed. Results: A high sensitivity and modest specificity were documented, and this later decreased during the COVID-19 outbreak, as well as its diagnostic accuracy. However, no significant differences were observed in the Area Under the Receiver Operating Characteristics among the analyzed periods. Conclusions: The evaluated case definition remains to be a cost-effective alternative to identify patients who may benefit from influenza-specific antiviral drugs, even during the COVID-19 global outbreak.


title: Preliminary study to identify severe from moderate cases of COVID-19 using NLR&RDW-SD combination parameter

text: Objectives: Investigate the characteristics and rules of hematology changes in patients with COVID-19, and explore the possibility to identify moderate and severe patients using conventional hematology parameters or combined parameters. Methods: The clinical data of 45 moderate and severe type patients with SARS-CoV-2 infections in Jingzhou Central Hospital from January 23 to February 13, 2020 were collected. The epidemiological indexes, clinical symptoms and laboratory test results of the patients were retrospectively analyzed. Those parameters with significant differences between the two groups were analyzed, and the combination parameters with best diagnostic performance were selected using the LDA method. Results: Of the 45 patients with COVID-19 (35 moderate and 10 severe cases), 23 were male and 22 female, aged 16-62 years. The most common clinical symptoms were fever (89%) and dry cough (60%). As the disease progressed, WBC, Neu#, NLR, PLR, RDW-CV and RDW-SD parameters in the severe group were significantly higher than that in the moderate group (P<0.05); meanwhile, Lym#, Eos#, HFC%, RBC, HGB and HCT parameters in the severe group were significantly lower than that in the moderate group (P<0.05). For NLR, the AUC, the best cut-off value, the sensitivity and the specificity were 0.890, 13.39, 83.3% and 82.4% respectively, and for PLR , the AUC, the best cut-off, the sensitivity and the specificity were 0.842, 267.03, 83.3% and 74.0% respectively. The combined parameter NLR&RDW-SD had the best diagnostic efficiency (AUC was 0.938) and when the cut-off value was 1.046, the sensitivity and the specificity were 90.0% and 84.7% respectively, followed by the fitting parameter NLR&RDW-CV (AUC = 0.923). When the cut-off value was 0.62, the sensitivity and the specificity for distinguishing severe type from moderate cases of COVID-19 were 90.0% and 82.4% respectively. Conclusions: The combined parameter NLR&RDW-SD is the best hematology index and can help clinicians to predict the severity of COVID-19 patients, and it can be used as a useful indicator to help prevent and control the epidemic.


title: Issue Cover

text: The cover image is based on the Editorial COVID-19 and liver disease by Luca Valenti, ALESSIO AGHEMO, Al0jando Forner et al , https://doi org/10 1111/liv 14470


title: Discovery of clinically approved drugs capable of inhibiting SARS-CoV-2 in vitro infection using a phenotypic screening strategy and network-analysis to predict their potential to treat covid-19

text: The disease caused by SARS-CoV2, covid-19, rapidly spreads worldwide, causing the greatest threat to global public health in the last 100 years. This scenario has become catastrophic as there are no approved vaccines to prevent the disease, and the main measures to contain the virus transmission are confinement and social distancing. One priority strategy is based on drug repurposing by pursuing antiviral chemotherapy that can control transmission and prevent complications associated with covid-19. With this aim, we performed a high content screening assay for the discovery of anti-SARS-CoV-2 compounds. From the 65 screened compounds, we have found four drugs capable to selectively inhibit SARS-CoV-2 in vitro infection: brequinar, abiraterone acetate, neomycin, and the extract of Hedera helix. Brequinar and abiraterone acetate had higher inhibition potency against SARS-CoV-2 than neomycin and Hedera helix extract, respectively. Drugs with reported antiviral activity and in clinical trials for covid-19, chloroquine, ivermectin, and nitazoxanide, were also included in the screening, and the last two were found to be non-selective. We used a data mining approach to build drug-host molecules-biological function-disease networks to show in a holistic way how each compound is interconnected with host node molecules and virus infection, replication, inflammatory response, and cell apoptosis. In summary, the present manuscript identified four drugs with active inhibition effect on SARS-CoV-2 in vitro infection, and by network analysis, we provided new insights and starting points for the clinical evaluation and repurposing process to treat SARS-CoV-2 infection. Summary sentence Discovery of drug repurposing candidates, inhibitors of SARS-CoV-2 infection in vitro, using a phenotypic screening strategy and network analysis.


title: Structure-Based Design, Synthesis and Biological Evaluation of Peptidomimetic Aldehydes as a Novel Series of Antiviral Drug Candidates Targeting the SARS-CoV-2 Main Protease

text: SARS-CoV-2 is the etiological agent responsible for the COVID-19 outbreak in Wuhan. Specific antiviral drug are urgently needed to treat COVID-19 infections. The main protease (Mpro) of SARS-CoV-2 is a key CoV enzyme that plays a pivotal role in mediating viral replication and transcription, which makes it an attractive drug target. In an effort to rapidly discover lead compounds targeting Mpro, two compounds (11a and 11b) were designed and synthesized, both of which exhibited excellent inhibitory activity with an IC50 value of 0.05 μM and 0.04 μM respectively. Significantly, both compounds exhibited potent anti-SARS-CoV-2 infection activity in a cell-based assay with an EC50 value of 0.42 μM and 0.33 μM, respectively. The X-ray crystal structures of SARS-CoV-2 Mpro in complex with 11a and 11b were determined at 1.5 Å resolution, respectively. The crystal structures showed that 11a and 11b are covalent inhibitors, the aldehyde groups of which are bound covalently to Cys145 of Mpro. Both compounds showed good PK properties in vivo, and 11a also exhibited low toxicity which is promising drug leads with clinical potential that merits further studies.


title: Validation of Remote Testing using BrainCheck, a Computerized Neurocognitive Test

text: Remote computerized neurocognitive testing (CNT) is a promising solution to have these assessments more accessible to a population facing a global pandemic and increased aging. BrainCheck (BC) is a CNT software available on iPhone, iPad, and computer browser, designed to fit the need for remote testing. Consistent measures across these varying platforms are necessary to ensure users have consistent cognitive assessments and results. We aimed to assess BC across all administration platforms and interactions to observe any differences in assessment performance. 75 participants were enrolled in the study and were divided into two groups: participants who took BC across multiple platforms and participants who took BC in both an administered and self-administered fashion. Here we found Stroop, Digit Symbol, and Trail A/B had significantly different performance across the platforms, while Flanker, Coordination, Matrix, Immediate and Delayed Recognitions did not. Also, we found that the test metrics did not show significant differences in performance between being administered and self-administering the test. We did observe quicker completion times during the second instance of the test when taken in quick succession (within a day apart, which would not be a typical clinical pattern) and despite this, composite scores did not change reflecting the resilience of BC to practice effects. In conclusion, our results demonstrate BC may be a robust, self-administered CNT solution with an appropriate adjustment for the platform used.


title: Is a COVID19 Quarantine Justified in Chile or USA Right Now?

text: During the current COVID-19 pandemic it is imperative to give early warnings to reduce mortality. However, non-specialist such as authorities and the general population face several problems to understand the real thread of this pandemic, and under/overestimation of its risk are a commonplace in the press and social media. Here we define an index, which we call the COVID-19 Burden Index, that relates the capacities of the healthcare system of a given country to treat severe and critical cases. Its value is 0 if there is no extra strain in the healthcare system, and it reaches 1.0 when the collapse is imminent. As of 23 March 2020, we show that Chile, the USA, UK, among other countries, must reduce the rate of infections right now, otherwise, in less than 7 days they could be in a catastrophic situation such as Italy, Spain and Iran.


title: COVID-19 Pandemic: Impact of Quarantine on Medical Students’ Mental Wellbeing and Learning Behaviors

text: BACKGROUND AND OBJECTIVES: The novel coronavirus COVID-19 pandemic causes great public health and socioeconomic harms. Worldwide many countries implemented quarantine policies to minimize the spread of this highly contagious disease. The present study aim was to investigate the impact of quarantine on the medical students’ mental wellbeing and learning behaviors. METHODS: In this descriptive study, we used a questionnaire with a Five-Point Likert Scale to collect the information. The questionnaire was distributed among 625 medical students through their emails with a response rate of 530 (84.8%), majority 294 (55.47%) being female. The survey questionnaire consisted of total 20 items; 12 items were related to psychological wellbeing and stress-allied queries and 08 items were about learning behaviors. RESULTS: The findings encompass two important characteristics related to quarantine, psychological wellbeing, and learning behaviors. A combined cohort of 234 medical students, either female or male, (which was 44.1% of the total responders) showed a sense of being emotionally detached from family, friends and fellow students, 125/ 530 (23.5%) medical students felt disheartened. Both female and male medical students showed a marked decrease in their overall work performance. Moreover, 56.2% of the total students (61.5% of the females and 49.5% of the males) felt a decrease in the time they spent studying. CONCLUSIONS: Both female and male medical students have identified that quarantine has caused them to feel emotionally detached from family, fellows, and friends and decrease their overall work performance and study period. The findings also show that one fourth of the medical students who participated in this study felt disheartened during the quarantine period. The long-term quarantine due to COVID-19 pandemics may causes further worsening in the psychological and learning behaviors of these medical students.


title: Estimating Preventable COVID19 Infections Related to Elective Outpatient Surgery in Washington State: A Quantitative Model

text: Background: As the number of suspected and confirmed COVID19 cases in the US continues to rise, the US surgeon general, Centers for Disease Control and Prevention, and several specialty societies have issued recommendations to consider canceling elective surgeries. However, these recommendations have also faced controversy and opposition. Objective: The goal of this study is to provide a quantitative analysis and model for preventable COVID19 infections from elective outpatient or ambulatory surgery cases, which can also be adapted to analyze COVID19 transmission in other healthcare settings. Furthermore, given the controversy over the appropriate handling of elective surgical cases during this pandemic, we hope that our results may have a positive impact on health policy and public health. Methods: Using previously published information on elective ambulatory or outpatient surgical procedures and publicly available data on COVID19 infections in the US and on the Diamond Princess cruise ship, we calculated a transmission rate and generated a mathematical model to predict a lower bound for the number of healthcare-acquired COVID19 infections that could be prevented by canceling or postponing elective outpatient surgeries in Washington state. Results: Our model predicts that over the course of 30 days, at least 2445 preventable patient infections and at least 1557 preventable healthcare worker (HCW) infections would occur in WA state alone if elective outpatient procedures were to continue as usual. The majority of these infections are caused by transmission from HCW who became infected at work. Conclusion: Given the large numbers of COVID19 infections that could be prevented by canceling elective outpatient surgeries, our findings support the recommendations of the US Surgeon General, CDC, American College of Surgeons (ACS), American Society of Anesthesiologists (ASA), and Anesthesia Patient Safety Foundation (APSF) to consider rescheduling or postponing elective surgeries until the COVID19 pandemic is under better control in the US.


title: Preventive strategy for tumor patients during COVID-19 pandemic/ 新型冠状病毒肺炎疫情下肿瘤患者的 感染防护策略

text: Tumor patients are the high risk population of being infected by SARS-CoV-2 during the COVID-19 pandemic. In order to reduce the infection risk of the tumor patients and maintain effective antitumor treatment, the preventive strategy for tumor patients in stationary phase, in treatment period, in immunosuppressor treatment, with fever, and involved in clinical trials, are discussed here with consideration of the disease features of the tumor patients and the experience of pharmaceutical care. In addition, suggestions regarding daily protection, diet and follow-up strategy for the tumor patients are provided.


title: Profiles of Social Distance Compliance: Psychological and Situational Predictors of Risky Behavior during COVID-19

text: The purpose of this study was to explore the factors underlying variability in compliance with CDC guidelines in response to the novel coronavirus, or COVID-19. To do this, we examined the frequency of once ordinary, but newly risky behavior (as deemed by CDC guidelines) in a sample of 482 MTurkers. We ran analyses probing the situational and dispositional variables that predicted variance in risky behavior using data-driven and hypothesis-generated approaches. We found situational and dispositional variables contributed unique variance to risky behavior, controlling for variability accounted for by demographic factors. More frequent report of risky activity was associated with higher extraversion, need for cognitive closure, behavior activation, and perceived resource scarcity; in contrast, more frequent report of risky activity was associated with less empathy and living space access, as well as younger age. To break down these findings, we used a cluster analysis to profile individuals, using only situational and dispositional variables belonging to seven clusters. Combined with testing differences in risk taking by cluster identity, we suggest this profile approach might allow consideration of multi-faceted attributes that influence adherence with public health guidance in the context of health emergencies like the COVID-19 pandemic.


title: A web survey to assess the use efficacy of personnel protective materials among allied health care workers during COVID-19 pandemic at North-East India

text: The rising pandemic is resulting in increased usage of personnel protective equipment in the hospital and community. The efficient and effective use of appropriate personal protective equipment will help assure its availability and healthcare provider safety. The purpose of this study was to assess the use efficacy of PPE among health care workers through a web based survey during the pandemic. the response rate of the survey was 66.75%. 35.2% gave a full rating on a point of 5 regarding the control measures taken by the hospital , 39% of respondents did not use the PPE, 90.6% used a surgical mask while 65.9% wore the disposable gloves and only 47.6% wore the goggles/face shield More than half the respondents did not wear the shoe-cover. 97.4% used the hand sanitizer and around 97% maintained hand hygiene practice.


title: Determinants of normal haemoglobin concentration among children in Ghana: a positive deviance analysis of nationally representative cross-sectional survey data

text: Anaemia among children under 5, is a public health problem of serious concern. In Ghana, 8 out of every 10 children are anaemic. This study employed a novel approach to investigate the determinants of normal haemoglobin (Hb) concentration among children aged 6 to 59 months, using data from the Ghana Demographic and Health Surveys. The results showed that a year change in maternal education was positively associated with normal Hb concentration. Children of non-anaemic mothers were 1.67 (CI=1.32, 2.10; P<.001) times more likely to have normal Hb concentration relative to children of anaemic mothers. Compared to mothers who had less than 4 antenatal care (ANC) visits, mothers who had at least 4 ANC visits increased the odds of their children having a normal Hb concentration by 1.62 (CI=1.09, 2.40; P<.018). Children living in middle and rich households had respectively 1.48 (CI=1.06, 2.07; p<.021) and 1.59 (CI=1.08, 2.33; p<.018) increased odds of having a normal Hb concentration relative to those living in poor households. Maternal education, anaemia, ANC attendance, and household wealth index are strong determinants of normal Hb concentration among children in Ghana. Strategies aimed at addressing childhood anaemia should take into account maternal anaemia, education, poverty and ANC attendance.


title: Spread and control of COVID-19 in China and their associations with population movement, public health emergency measures, and medical resources

text: ABSTRACT BACKGROUND The COVID-19 epidemic, first emerged in Wuhan during December 2019, has spread globally. While the mass population movement for Chinese New Year has significantly influenced spreading the disease, little direct evidence exists about the relevance to epidemic and its control of population movement from Wuhan, local emergency response, and medical resources in China. METHODS Spearman's correlation analysis was performed between official data of confirmed COVID-19 cases from Jan 20th to Feb 19th, 2020 and real-time travel data and health resources data. RESULTS There were 74,675 confirmed COVID-19 cases in China by Feb 19th, 2020. The overall fatality rate was 2.84%, much higher in Hubei than in other regions (3.27% vs 0.73%). The index of population inflow from Hubei was positively correlated with total (Provincial r=0.9159, p<0.001; City r=0.6311, p<0.001) and primary cases (Provincial r=0.8702, p<0.001; City r=0.6358, p<0.001). The local health emergency measures (eg, city lockdown and traffic control) were associated with reduced infections nationwide. Moreover, the number of public health employees per capita was inversely correlated with total cases (r=-0.6295, p<0.001) and infection rates (r=-0.4912, p<0.01). Similarly, cities with less medical resources had higher fatality (r=-0.4791, p<0.01) and lower cure rates (r=0.5286, p<0.01) among the confirmed cases. CONCLUSIONS The spread of the COVID-19 in China in its early phase was attributed primarily to population movement from Hubei, and effective governmental health emergency measures and adequate medical resources played important roles in subsequent control of epidemic and improved prognosis of affected individuals.


title: Environmental indicator for effective control of COVID-19 spreading

text: Recently, a novel coronavirus (COVID-19) has caused viral pneumonia worldwide, spreading to more than 200 countries, posing a major threat to international health. To prevent the spread of COVID-19, in this study, we report that the city lockdown measure was an effective way to reduce the number of new cases, and the nitrogen dioxide (NO2) concentration can be adopted as an environmental lockdown indicator. In China, after strict city lockdown, the average NO2 concentration decreased 55.7% (95% confidence interval (CI): 51.5-59.6%) and the total number of confirmed new cases decreased significantly. We also determined that the global airborne NO2 concentration steeply decreased over the vast majority of COVID-19-hit areas based on satellite measurements. We found that if NO2 emissions significantly decreased, the total number of confirmed new cases reached an inflection point after approximately two weeks. Italy, Germany and France are good examples. Our results suggest that NO2 satellite measurement can help decision makers effectively monitor control regulations to reduce the spread of COVID-19.


title: The Effect of Anti-COVID-19 Policies on the Evolution of the Disease: A Complex Network Analysis of the Successful Case of Greece

text: Within the context of Greece promising a success story in the fight against the disease, this paper proposes a novel method for studying the evolution of the Greek COVID-19 infection curve in relation to the anti-COVID-19 policies applied to control the pandemic Based on the ongoing spread of COVID-19 and the insufficient data for applying classic time-series approaches, the analysis builds on the visibility graph algorithm to study the Greek COVID-19 infection curve as a complex network By using the modularity optimization algorithm, the generated visibility graph is divided into communities defining periods of different connectivity in the time-series body These periods reveal a sequence of different typologies in the evolution of the disease, starting with a power pattern, where a second order polynomial (U-shaped) pattern intermediates, being followed by a couple of exponential patterns, and ending up with a current logarithmic pattern revealing that the evolution of the Greek COVID-19 infection curve tends towards saturation In terms of Gaussian modeling, this successive compression of the COVID-19 infection curve into five parts implies that the pandemic in Greece is about to reach the second (decline) half of the bell-shaped distribution The network analysis also illustrates stability of hubs and instability of medium and low-degree nodes, implying a low probability of meeting maximum (infection) values in the future and high uncertainty in the variability of other values below the average The overall approach contributes to the scientific research by proposing a novel method for the structural decomposition of a time-series into periods, which allows removing from the series the disconnected past-data facilitating better forecasting, and provides insights of good policy and decision-making practices and management that may help other countries improve their performance in the war against COVID-19


Addressing mental health needs: an integral part of COVID-19 response


title: Age differences in clinical features and outcomes in patients with COVID-19, Jiangsu, China: a retrospective, multi-center cohort study

text: Objectives To determine the age-specific clinical presentations and incidence of adverse outcomes among patients with COVID-19 in Jiangsu, China. Design and setting This is a retrospective, multi-center cohort study performed at twenty-four hospitals in Jiangsu, China. Participants From January 10 to March 15, 2020, 625 patients with COVID-19 were involved. Results Of the 625 patients (median age, 46 years; 329 [52.6%] males), 37 (5.9%) were children (18 years or less), 261 (40%) young adults (19-44 years), 248 (39.7%) middle-aged adults (45-64 years), and 79 (12.6%) elderly (65 years or more). The incidence of hypertension, coronary heart disease, chronic obstructive pulmonary disease, and diabetes comorbidities increased with age (trend test, P < .0001, P = 0.0003, P < .0001, and P < .0001 respectively). Fever, cough, and shortness of breath occurred more commonly among older patients, especially the elderly, compared to children (Chi-square test, P = 0.0008, 0.0146, and 0.0282, respectively). The quadrant score and pulmonary opacity score increased with age (trend test, both P < .0001). Older patients had significantly more abnormal values in many laboratory parameters than younger patients. Elderly patients contributed the highest proportion of severe or critically-ill cases (33.0%, Chi-square test P < 0.001), intensive care unit (ICU) (35.4%, Chi-square test P < 0.001), and respiratory failure (31.6%, Chi-square test P = 0.0266), and longest hospital stay (21 days, ANOVA-test P < 0.001). Conclusions Elderly ([≥]65) patients with COVID-19 had the highest risk of severe or critical illness, intensive care use, respiratory failure, and the longest hospital stay, which may be due partly to that they had higher incidence of comorbidities and poor immune responses to COVID-19.


title: Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease

text: The emergence of SARS-CoV-2 has created an international health crisis. Small animal models mirroring SARS-CoV-2 human disease are essential for medical countermeasure (MCM) development. Mice are refractory to SARS-CoV-2 infection due to low affinity binding to the murine angiotensin-converting enzyme 2 (ACE2) protein. Here we evaluated the pathogenesis of SARS-CoV-2 in male and female mice expressing the human ACE2 gene under the control of the keratin 18 promotor. In contrast to non-transgenic mice, intranasal exposure of K18-hACE2 animals to two different doses of SARS-CoV-2 resulted in acute disease including weight loss, lung injury, brain infection and lethality. Vasculitis was the most prominent finding in the lungs of infected mice. Transcriptomic analysis from lungs of infected animals revealed increases in transcripts involved in lung injury and inflammatory cytokines. In the lower dose challenge groups, there was a survival advantage in the female mice with 60% surviving infection whereas all male mice succumbed to disease. Male mice that succumbed to disease had higher levels of inflammatory transcripts compared to female mice. This is the first highly lethal murine infection model for SARS-CoV-2. The K18-hACE2 murine model will be valuable for the study of SARS-CoV-2 pathogenesis and the assessment of MCMs.


title: A unified activities-based approach to the modelling of viral epidemics and COVID-19 as an illustrative example

text: A new approach to formulating mathematical models of increasing complexity to describe the dynamics of viral epidemics is proposed. The approach utilizes a map of social interactions characterizing the population and its activities and, unifying the compartmental and the stochastic viewpoints, offers a framework for incorporating both the patterns of behaviour studied by sociological surveys and the clinical picture of a particular infection, both for the virus itself and the complications it causes. The approach is illustrated by taking a simple mathematical model developed in its framework and applying it to the ongoing pandemic of SARS-CoV-2 (COVID-19), with the UK as a representative country, to assess the impact of the measures of social distancing imposed to control its course.


title: The lockdown of Hubei Province causing different transmission dynamics of the novel coronavirus (2019-nCoV) in Wuhan and Beijing

text: Background: After the outbreak of novel coronavirus (2019-nCoV) starting in late 2019, a number of researchers have reported the predicted the virus transmission dynamics. However, under the strict control policy the novel coronavirus does not spread naturally outside Hubei Province, and none of the prediction closes to the real situation. Methods and findings: We used the traditional SEIR model, fully estimated the effect of control measures, to predict the virus transmission in Wuhan, the capital city of Hubei Province, and Beijing. We forecast that the outbreak of 2019-nCoV would reach its peak around March 6±10 in Wuhan and March 20±16 in Beijing, respectively. The infectious population in Beijing would be much less (only 0.3%) than those in Wuhan at the peak of this transmission wave. The number of confirmed cases in cities inside Hubei Province grow exponentially, whereas those in cities outside the province increase linearly. Conclusions: The unprecedented province lockdown substantially suspends the national and global outbreak of 2019-nCoV.


title: How Essential Is to Focus on Physician's Health and Burnout in Coronavirus (COVID-19) Pandemic?

text: An infection of novel coronavirus (COVID-19) that originated from Wuhan city of China in December 2019 converted rapidly into pandemic by March 11, 2020. To date, the number of confirmed cases and deaths has risen exponentially in more than 200 countries, with an estimated crude mortality ratio of at least over 2%. The unpreparedness to tackle the unprecedented situation of coronavirus has contributed to the rising number of cases, which has generated an immense sense of fear and anxiety amongst the public. It has further resulted in the inadequacy and unavailability of essential medical supplies, physicians, and healthcare workers (HCW). Although the chief focus is on minimizing transmission through prevention, combating infection, and saving lives by ramping up the development of treatment and vaccines, very little attention is on the critical issue of physician burnout, resident burnout, and the psychological well-being of HCW. Until now, no significant steps have been taken by the authorities to minimize the COVID-19 specific contributing factors for burnout. The COVID-19 has posed strain on the entire healthcare system already, and it is vital to remediate the issue of physician and resident burnout urgently with concrete actions to avoid subsequent potential short-term and long-term adverse implications.


title: Forecasting the Number of Coronavirus (COVID-19) Cases in Ethiopia Using Exponential Smoothing Times Series Model

text: The main objective of this study is to forecast COVID-19 case in Ethiopiausing the best-fitted model. The time series data of COVID-19 case in Ethiopia from March 14, 2020 to June 05, 2020 were used.To this end, exponential growth, single exponential smoothing method, and doubleexponential smoothing methodwere used. To evaluate the forecasting performance of the model, root mean sum of square error was used. The study showed that double exponential smoothing methods was appropriate in forecasting the future number ofCOVID-19 cases in Ethiopia as dictated by lowest value of root mean sum of square error. The forecasting model shows that the number of coronavirus cases in Ethiopia grows exponentially. The finding of the results would help the concerned stakeholders to make the right decisions based on the information given on forecasts.