title: Using Feedback on Symptomatic Infections to Contain the Coronavirus Epidemic: Insight from a SPIR Model

text: A study is presented on the use of real-time information about symptomatic infectious individuals to adjust restrictions of human contacts at two basic levels, the stricter being on the symptomatic infectious group. Explicit analytical formulas as well as numerical results are presented to rapidly elucidate what-if questions on averting resurgence of the coronavirus epidemic after the first wave wanes. Implementation of related ideas would rely on a mix of several factors, including personal initiative and sophisticated technology for monitoring and testing. For robust decision making on the subject, detailed multidisciplinary studies remain indispensable.


title: A phased approach to unlocking during the COVID-19 pandemic; Lessons from trend analysis

text: With the COVID-19 pandemic leading to radical political control of social behaviour, including restricted movement outsides homes. Can more detailed analysis of the published confirmed local case data from the pandemic in England using infection ratio and comparing local level data provide a deeper understanding of the wider community infection and inform the future unlocking process. The historic daily published 78,842 confirmed cases in England up to 13/4/2020 in each of 149 Upper Tier Local Authority (UTLA) were converted to Average Daily Infection Rate (RADIR), an R-value - the number of further people infected by one infected person after their 5-day incubation and during their 5-day infectious phase, and the associated Rate of Change of Infection Rate (δIR) also calculated. Results compared to look for significant variances between regions. Stepwise regression was carried out to see what local factors could be linked to the difference in local infection rates. The peak of COVID-19 infection has passed. The current RADIR is now below 1. The rate of decline is such that within 14 days it may be below 0.5. There are significant variations in the current RADIR and δIR between the UTLAs, suggesting that the disease locally may be at different stages. Regression analysis across UTLAs found that the only factor that could be related to the fall in RADIR was an increase in the number of confirmed infection/1,000 population. Extrapolation of these results showed that based on assuming a link to increased immunity, unreported community infection may be over 200 times higher than the reported confirmed cases providing evidence that by the end of the second week in April 26% of the population may already have had the disease and so now have increased immunity. Linking these increased estimated infected numbers to recorded deaths indicates a possible mortality rate of 0.14%. Analysis of the current reported local case data using the infectious ratio does provide greater insight into the current levels of community infection and can be used to make better-informed decisions about the future management of restricted social behaviour and movement


title: The attitudes, perceptions and experiences of medical school applicants following the closure of schools and cancellation of public examinations in 2020 due to the COVID-19 pandemic

text: Objective To describe medical applicants' experiences of education and their views on changes to medical school admissions, including the awarding of calculated grades, following the 2020 closure of schools and universities, and the cancellation of public examinations in the United Kingdom due to the COVID-19/coronavirus pandemic. To understand how applicants from diverse social backgrounds might differ in these regards. Design Cross-sectional questionnaire study forming part of the longitudinal United Kingdom Medical Applicant Cohort Study (UKMACS). Setting United Kingdom medical school admissions. Participants 2887 participants (68% female; 64% with at least one degree-educated parent; 63% with at least one parent in the highest socioeconomic group) completed an online questionnaire between 8th and 22nd April 2020. To be invited to complete the questionnaire, participants had to have registered to take the University Clinical Admissions Test (UCAT) in 2019 and to have agreed to be invited to take part in the study, or they needed to have completed one or more previous UKMACS questionnaires. They also need to have been seriously considering applying to study medicine in the UK for entry in 2020 between May and October 2019, and be resident in the UK or Islands/Crown Dependencies. Main outcome measures Views on calculated grades, views on potential changes to medical school admissions and teaching in 2020 and 2021, reported experiences of education following the closure of educational institutions in March 2020. Results Respondents had concerns about the calculated grades that will replace A-level examinations, especially female applicants and applicants from Black Asian and Minority Ethnic (BAME) backgrounds who felt teachers would find it difficult to grade and rank students accurately, as well as those from non-selective state schools and those living in deprived areas who had some concerns about the grade standardisation process. Calculated grades were not considered fair enough by a majority to use in the acceptance or rejection of medical offer-holders, but several measures - including interview and aptitude test scores - were considered fair enough to use in combination. Respondents from non-selective state (public) schools reported less use of and less access to educational resources compared to their counterparts at private/selective schools. In particular they reported less online teaching in real time, and reported spending less time studying during the lockdown. Conclusions The coronavirus pandemic will have significant and long term impacts on the selection, education and performance of our future medical workforce. It is important that the views and experiences of medical applicants from diverse backgrounds are taken into consideration in decisions affecting their futures and the future of the profession.


title: Can N95 respirators be reused after disinfection? And for how many times?

text: The Coronavirus Disease 2019 (COVID-19) pandemic has led to a major shortage of N95 respirators, which protect healthcare professionals and the public who may come into contact with the virus. It is necessary to determine the conditions that would allow the safe reuse respirators and personal protection in this crisis. We found that heating (<100 {degrees}C) under various humidities (up to 100% RH at 75 {degrees}C) and ultraviolet (UV) irradiation were the most promising candidates for mask reuse in the modern hospital infrastructure (up to 20 cycles), when tested on a fabric with particle filtration efficiency [≥]95%. Treatments involving certain liquids and vapors may require caution, as steam, alcohol, and bleach all led to degradation in filtration efficiency, leaving the user vulnerable to viral aerosols.


title: Evaluation of the US governors decision when to issue stay-at-home orders

text: Objectives To evaluate if the US governors decision to issue the stay-at-home orders reflects the classic Weber-Fechner law of psychophysics, the amount by which a stimulus (such as number of cases or deaths) must increase in order to be noticed-the just noticeable difference- as a fraction of the intensity of that stimulus. Design A prospective observational study using data on the daily number of infected patients and deaths from the New York Times daily database. Setting 50 States and the District of Columbia Participants All individuals judged to be positive for the coronavirus or to have died from COVID19. Main outcome measures Number of people diagnosed with or died from COVID19. Results We found that the decision to issue the state-at-home order reflects the Weber-Fechner law of psychophysics. Both the number of infections (p=<0.0001; R2=0.79) and deaths (p<0.0001; R2=0.63) were highly statistically significantly associated with the decision to issue the stay-at-home orders. The results indicate that for each doubling of infections or deaths within their state, an additional four to six governors will issue the stay-at-home order. We also observed a clear dose-response relationship in the Cox model: the larger the number of cases, or deaths, the higher the probability that the stay-at-home order will be made. When the number of deaths reached 256 or the number of infected people was greater than 16,384, the probability of issuing a stay-at-home order was close to 100%. Conclusions When there are not clearly articulated rules to follow, decision-makers in times of crisis such as COVID19 resort to use of simple heuristics consistent with the Weber-Fechner law of psychophysics. The findings are important for the public to understand how their elected officials make important public health decisions.


title: Opinions from the epicenter: an online survey of university students in Wuhan amidst the COVID-19 outbreak11

text: The outbreak of the novel coronavirus (2019-nCov, COVID) in Wuhan, China, in December 2019 quickly escalated into a global health emergency. This study seeks to investigate the attitudinal and behavioral patterns of university students in Wuhan, the epicenter. Conducted in late January 2020, an online survey collected data from more than 8000 students of four elite national universities located in Wuhan. The students sampled included both Wuhan natives and non-locals who returned home in the early stages of the outbreak. The study notes widespread psychological stress among students but positive behavioral compliance with personal hygiene practices. Official announcements were the chief source of information for the respondents, who also demonstrated high demand for transparency of information disclosure. Some highly tight anti-epidemic measures were found at the local level. Albeit aggressive to certain extent, they may be necessary under such critical circumstances. The respondents offered varying evaluations of the performance of central government, local governments, civil society, and the health system in this public health crisis. The article concludes with policy implications and caveats.


Systematic Screening for Venous Thromboembolic Events in COVID-19 Pneumonia


Breaking News: ‘Don't You Think This Whole COVID-19 Thing is Overblown?’


Small Study Finds Remdesivir Benefit in COVID-19 But Questions Remain


title: Holder Pasteurization Inactivates SARS-CoV-2 in Human Breast Milk

text: SARS-CoV-2 RNA has been detected in the human breast milk of infected mothers, raising concerns regarding the safety of breastfeeding upon infection. We here show that holder pasteurization inactivates SARS-CoV-2 and provides an alternative and safe option for infected mothers to continue feeding breast milk to their infants.


title: COVID-19: Recent updates on SARS-CoV-2 and Preventing its Community Transmission in India by 21 Days Lockdown

text: The current pandemic of COVID-19 has caused havoc all over world since its emergence and rapid spread Within three months the virus SARS-CoV-2 which was isolated from pneumonia cases in Wuhan City, Hubei Province, China in late December 2019, has affected almost all countries India reported its first case of COVID-19 from state of Kerala on January 30, 2020, a student returned from city of Wuhan Till date in India the disease had affected 12759 patients with 420 deaths With every passing day the mysterious virus is been uncovered with its unique characteristics enabling the researcher to unfold the various methods including hand washing and social distancing to curtail the pandemic Measures like 21 days lockdown to certain extent are effective but considering asymptomatic spreaders, extended measured lockdowns will be useful in the long term war against COVID-19 Till the vaccine and therapeutic solutions are derived, answer to pandemic and SARS-CoV-2 lies in lockdown, social distancing, contact tracing and containment


title: Macropahge expression and prognostic significance of the long pentraxin PTX3 in COVID-19

text: PTX3 is an essential component of humoral innate immunity, involved in resistance to selected pathogens and in the regulation of inflammation. PTX3 plasma levels are associated with poor outcome in systemic inflammatory conditions and vascular pathology. The present study was designed to assess expression and significance of PTX3 in COVID-19. By bioinformatics analysis of public databases PTX3 expression was detected in lung respiratory cell lines exposed to SARS-CoV-2. By analysis at single cell level of COVID-19 circulating mononuclear cells, we found that PTX3 was selectively expressed by monocytes among circulating leukocytes. Moreover, in lung bronchoalveolar lavage fluid, single cell analysis revealed selective expression of PTX3 in neutrophils and macrophages, which play a major role in the pathogenesis of the disease. By immunohistochemistry, PTX3 was expressed by lung myelomocytic cells, type 2 pneumocytes and vascular endothelial cells. PTX3 plasma levels were determined by ELISA in 96 consecutive patients with a laboratory-confirmed diagnosis of COVID-19. Higher PTX3 plasma levels were observed in 52 (54.2%) patients admitted in ICU (median 21.0ng/mL, IQT 15.5-46.3 vs 12.4ng/mL IQT 6.1-20.2 in ward patients; p=0.0017) and in 22 (23%) patients died by 28 days (39.8ng/mL, IQT 20.2-75.7 vs 15.7ng/mL, IQT 8.2-21.6 in survivors; p=0.0001). After determining an optimal PTX3 cut-off for the primary outcome, the Kaplan-Meier curve showed an increased mortality in patients with PTX3>22.25ng/mL (Log-rank tests p<0.0001). In Cox regression model, PTX3>22.25ng/mL showed an adjusted Hazard Ratio (aHR) of 7.6 (95%CI2.45-23.76) in predicting mortality. Performing a multivariate logistic regression including all inflammatory markers (PTX3, ferritin, D-Dimer, IL-6, and CRP), PTX3 was the only marker significantly associated with death (aHR 1.13;95%CI1.02-1.24; p=0.021). The results reported here suggest that circulating and lung myelomonocytic cells are a major source of PTX3 and that PTX3 plasma levels can serve as a strong prognostic indicator of short-term mortality in COVID-19.


docid: gfjbsheq

title: The Need for a Mental Health Technology Revolution in the COVID-19 Pandemic


title: Rapid point of care nucleic acid testing for SARS-CoV-2 in hospitalised patients: a clinical trial and implementation study

text: Objective To compare a point of care (POC) nucleic acid amplification based platform for rapid diagnosis of COVID-19 against the standard laboratory RT-PCR test and perform an implementation study. Design: prospective clinical trial (COVIDx) and observational study Setting: a large UK teaching hospital Participants: patients presenting to hospital with possible COVID-19 disease and tested on a combined nasal/throat swab using the SAMBA II SARS-CoV-2 rapid POC test and in parallel a combined nasal/throat swab for standard lab RT-PCR testing. Implementation phase participants underwent SARS-CoV-2 POC testing for a range of indications over a ten day period pre and post SAMBA II platform implementation. Main outcome measures: concordance and sensitivity and specificity of POC using the lab test as the reference standard, test turnaround time in trial and implementation periods; time to definitive patient triage from ED, time spent on COVID-19 holding wards, bay closures avoided, proportions of patients in isolation rooms following test, proportions of patients able to be moved to COVID negative areas following test. Results 149 participants were included in the COVIDx trial. 32 (21.5%) tested positive and 117 (78.5%) tested negative by standard lab RT-PCR. Median age was 62.7 (IQR 37 to 79) years and 47% were male. Cohen's kappa correlation between the index and reference tests was 0.96, 95% CI (0.91, 1.00). Sensitivity and specificity of SAMBA against the RT-PCR lab test were 96.9% (95% CI 0.838-0.999) and 99.1% (0.953-0.999) respectively. Median time to result was 2.6 hours (IQR 2.3 to 4.8) for SAMBA II and 26.4 hours (IQR 21.4 to 31.4) for the standard lab RT-PCR test (p<0.001). In the first 10 days of the SAMBA II SARS-CoV-2 test implementation for all hospital COVID-19 testing, analysis of the first 992 tests showed 59.8% of tests were used for ED patients, and the remainder were done for pre-operative screening (11.3%), discharges to nursing homes (10%), in-hospital screening of new symptoms (9.7%), screening in asymptomatic patients requiring hospital admission screening (3.8%) and access to interventions such as dialysis and chemotherapy for high risk patients (1.2%). Use of single occupancy rooms amongst those tested fell from 30.8% before to 21.2% after testing (p=0.03). 11 bay closures were avoided by use of SAMBA over ten days. The post implementation group was then compared with 599 individuals who had a standard lab RT-PCR test in the 10 days prior to SAMBA introduction. Median time to result during implementation fell from 39.4 hours (IQR 24.7-51.3) to 3.6 hours (IQR 2.6-5.8), p<0.0001 and the median time to definitive ward move from ED was significantly reduced from 24.1 hours (9.2-48.6) to 18.5 hours (10.2-28.8), p=0.002. Mean length of stay on a COVID-19 holding ward decreased from 58.5 hours to 29.9 hours (p<0.001) compared to the 10 days prior to implementation. Conclusions SAMBA II SARS-CoV-2 rapid POC test performed as well as standard lab RT-PCR and demonstrated shorter time to result both in trial and real-world settings. It was also associated with faster time to triage from the ED, release of isolation rooms, avoidance of hospital bay closures and movement of patients to COVID negative open green category wards, allowed discharge to care homes and expediting access to hospital investigations and procedures. POC testing will be instrumental in mitigating the impact of COVID-19 on hospital systems by allowing rapid triage and patient movement to safe and appropriate isolation wards in the hospital. This is also likely to reduce delays in patients accessing appropriate investigation and treatment, thereby improving clinical outcomes.


title: Coronavirus-nephropathy; renal involvement in COVID-19

text: Renal disturbances by coronavirus disease 2019 (COVID-19), consisted of acute kidney injury, due to acute tubular necrosis induced by sepsis, hydration, cytokine storm syndrome, rhabdomyolysis and hypoxia. As the direct cytopathic effect of virus on various renal cells has been detected in previous studies, direct virus invasion to the renal tubular cells and interstitium or glomeruli is possible. Previous studies showed that coronavirus enters into the cells by angiotensin-converting enzyme II receptors that are extensively presented in the renal cells. Further, acute kidney injury in COVID-19 is strongly associated with higher mortality and morbidity and is an indicator for survival with Coronavirus infection. In the overall approach to patients with COVID-19 infection, special attention should be paid to control of classical risk factors of kidney injury.


title: Coronavirus activates a stem cell-mediated defense mechanism that reactivates dormant tuberculosis: implications in COVID-19 pandemic

text: We postulate that similar to bacteria, adult stem cells may also exhibit an innate defense mechanism to protect their niche. Here, we provide preliminary data on stem cell based innate defense against a mouse model of coronavirus, murine hepatitis virus-1 (MHV-1) infection. In a mouse model of mesenchymal stem cell (MSC) mediated Mycobacterium tuberculosis (Mtb) dormancy, MHV-1 infection in the lung exhibited 20 fold lower viral loads than the healthy control mice, suggesting the potential enhancement of an anti-MHV-1 defense by Mtb. This defense mechanism involves the in vivo expansion and reprogramming of CD271+MSCs in the lung to an enhanced stemness phenotype. The reprogrammed MSCs facilitate the activation of stemness genes, intracellular Mtb replication, and extracellular release of Mtb. The conditioned media of the reprogrammed MSCs exhibit direct anti-viral activity in an in vitro model of MHV-1 induced toxicity to type II alveolar epithelial cells. Thus, our data suggest that reprogrammed MSCs exert a unique innate defense against MHV-1 by activating dormant Mtb. The molecular details of this anti-viral defense mechanism against coronavirus could be further studied to develop a vaccine against COVID-19.


title: Distinguishing L and H phenotypes of COVID-19 using a single x-ray image

text: Recent observations have shown that there are two types of COVID-19 response: an H phenotype with high lung elastance and weight, and an L phenotype with low measures. H-type patients have pneumonia-like thickening of the lungs and require ventilation to survive; L-type patients have clearer lungs that may be injured by mechanical assistance. As treatment protocols differ between the two types, and the number of ventilators is limited, it is vital to classify patients appropriately. To date, the only way to confirm phenotypes is through high-resolution computed tomography. Here, we identify L- and H-type patients from their frontal chest x-rays using feature-embedded machine learning. We then apply the categorization to multiple images from the same patient, extending it to detect and monitor disease progression and recovery. The results give an immediate criterion for coronavirus triage and provide a methodology for respiratory diseases beyond COVID-19.


title: On the assessment of more reliable COVID-19 infected number: the italian case.

text: COVID-19 (SARS-CoV-2) is the most recent pandemic disease the world is currently managing. It started in China at the end of 2019, and it is diffusing throughout Italy, one of the most affected countries, and it is currently spreading through European countries and USA. Patients affected by COVID-19 are identified employing medical swabs applied mainly to (i) citizens with COVID-19 symptoms such as flu or high temperature, or (ii) citizens that had contacts with COVID-19 patients. A percentage of COVID-19 affected patients needs hospitalisation, whereas a portion needs to be treated in Intensive Care Units (ICUs). Nevertheless, it is a matter of current intuition that COVID-19 infected citizens are more than those detected, and sometime the infection is detected too late. Thus there are many efforts in both tracking people activities as well as diffusing low cost reliable COVID-19 tests for early detection. Starting from mortality rates of diseases caused by viruses in the same family (e.g. MERS, SARS, H1N1), we study the relations between the number of COVID-19 infections and the number of deaths, through Italian regions. We thus assess several infections being higher than the ones currently measured. We thus focus on the characterisation of the pandemic diffusion by estimating the infected number of patients versus the number of death. We use such an estimated number of infections, to foresee the effects of restriction actions adopted by governments to constrain virus diffusion. We finally think that our model can support the healthcare system to react when COVID-19 is increasing.


title: Insights into The Codon Usage Bias of 13 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Isolates from Different Geo-locations

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of Coronavirus disease 2019 (COVID-19) which is an infectious disease that spread throughout the world and was declared as a pandemic by the World Health Organization (WHO). In the present study, we analyzed genome-wide codon usage patterns in 13 SARS-CoV-2 isolates from different geo-locations (countries) by utilizing different CUB measurements. Nucleotide and di-nucleotide compositions displayed bias toward A/U content in all codon positions and CpU-ended codons preference, respectively. Relative Synonymous Codon Usage (RSCU) analysis revealed 8 common putative preferred codons among all the 13 isolates. Interestingly, all of the latter codons are A/U-ended (U-ended: 7, A-ended: 1). Cluster analysis (based on RSCU values) was performed and showed comparable results to the phylogenetic analysis (based on their whole genome sequences) indicating that the CUB pattern may reflect the evolutionary relationship between the tested isolates. To investigate the force (mutation and/or selection) influencing the pattern of CUB in SARS-CoV-2 coding sequences, we employed the following; (i). Effective number of codons (ENc), (ii). ENc-GC3 plot, (iii). Neutrality plot, and (iv) Codon adaptation index (CAI). According to their results, natural selection and/or other factors (not investigated in this study) may be the dominant force driving SARS-CoV-2 CUB. It is also worth mentioning that, by using the most expressed genes in human lung tissues as a reference set, some viral genes such as Nucleocapsid phosphoprotein, ORF7a protein, and surface glycoprotein had high CAI values which may indicate for selection force acting on their codon usage, as they play important roles in viral assembly and may help viruses avoid the host immune system. The outcome of our study may help in understanding the underlying factors involved in the evolution of SARS-CoV-2 viruses, and the interactions with their host. Also, it may aid in vaccine design strategies.


docid: ufcvecwo

title: Outcome reporting from protocols of clinical trials of Coronavirus Disease 2019 (COVID-19): a review

text: Objectives: To examine heterogeneity of outcomes in protocols of clinical trials of Coronavirus Disease 2019 (COVID-19) and to identify outcomes for prioritization in developing a core outcome set (COS) in this field. Design: This study is a review. Data sources: Databases of ICMJE-accepted clinical trial registry platform were searched on February 14, 2020. Eligibility Criteria: Randomized controlled trials (RCTs) and non-RCTs of COVID-19 were considered.Conditions of patients include common type, severe type or critical type. Interventions include traditional Chinese medicine (TCM) and Western medicine. We excluded trials that for discharged patients, psychological intervention and complications of COVID-19. Data extraction and synthesis: The general information and outcomes, outcome measurement instruments and measurement times were extracted. The results were analysed by descriptive analysis. Results: 19 registry platforms were searched. A total of 97 protocols were included from 160 protocols. For protocols of TCM clinical trials, 76 outcomes from 16 outcome domains were reported, and almost half (34/76, 44.74%) of outcomes were reported only once; the most frequently reported outcome was time of SARS-CoV-2 RNA turns to negative. 27 (27/76, 35.53%) outcomes were provided one or more outcome measurement instruments. 10 outcomes were provided one or more measurement time frame. For protocols of western medicine clinical trials, 126 outcomes from 17 outcome domains were reported; almost half (62/126, 49.21%) of outcomes were reported only once; the most frequently reported outcome was proportion of patients with negative SARS-CoV-2. 27 outcomes were provided one or more outcome measurement instruments. 40 (40/126, 31.75%) outcomes were provided one or more measurement time frame. Conclusion: Outcome reporting in protocols of clinical trials of COVID-19 is inconsistent. Thus, developing a core outcome set is necessary. Keywords: Outcomes; clinical trials, COVID-19; review.


title: Association between ABO blood groups and clinical outcome of coronavirus disease 2019: Evidence from two cohorts

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the third most common coronavirus that causes large-scale infections worldwide. The correlations between pathogen susceptibility and blood type distribution have attracted attention decades ago. The current retrospective study aimed to examine the correlation between blood type distribution and SARS-CoV-2 infection, progression, and prognosis in patients with coronavirus disease 2019 (COVID-19). With 265 patients from multiple medical centers and two established cohorts, we found that the blood type A population was more sensitive to SARS-CoV-2. Moreover, the blood type distribution was not relevant to acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), and mortality in COVID-19 patients. These findings are indicative of coping with the great threat since it probed the relationship between blood types and ARDS, AKI, and mortality, in addition to susceptibility in COVID-19 patients.


docid: zugrtvyo

title: Intra-host site-specific polymorphisms of SARS-CoV-2 is consistent across multiple samples and methodologies

text: Despite the potential relevance to clinical outcome, intra-host dynamics of SARS-CoV-2 are unclear. Here, we quantify and characterize intra-host variation in SARS-CoV-2 raw sequence data uploaded to SRA as of 14 April 2020, and compare results between two sequencing methods (amplicon and RNA-Seq). Raw fastq files were quality filtered and trimmed using Trimmomatic, mapped to the WuhanHu1 reference genome using Bowtie2, and variants called with bcftools mpileup. To ensure sufficient coverage, we only included samples with 10X coverage for >90% of the genome (n=406 samples), and only variants with a depth >=10. Derived (i.e. non-reference) alleles were found at 408 sites. The number of polymorphic sites (i.e. sites with multiple alleles) within samples ranged from 0-13, with 72% of samples (295/406) having at least one polymorphic site. Correlation between number of polymorphic sites and coverage was very low for both sequencing methods (R2 < 0.1, p < 0.05). Polymorphisms were observed >1 sample at 66 sites (range: 2-38 samples). The minor allele frequency (MAF) at each shared polymorphic site was 0.03% - 48.5%. 33/66 sites occurred in ORF1a1b, and 37/66 changes were non-synonymous. At 10/66 sites, derived alleles were found in samples sequenced using both methods. Polymorphic amplicon samples were found at 10/10 positions, while polymorphic RNA-Seq samples were found at 7/10 positions. In conclusion, our results suggest that intra-host variation is prevalent among clinical samples. While mutations resulting from amplification and/or sequencing errors cannot be excluded, the observation of shared polymorphic sites with high MAF across multiple samples and sequencing methods is consistent with true underlying variation. Further investigation into intra-host evolutionary dynamics, particularly with longitudinal sampling, is critical for broader understanding of disease progression.


docid: dibfdkzk

title: A facile method of mapping neutralizing HIV-1 epitopes

text: Identification of specific epitopes targeted by neutralizing antibodies is essential to advance epitope-based vaccine design strategies. We report a methodology for rapid epitope mapping of neutralizing antibodies against HIV-1 Env at single residue resolution, using viral neutralization assays and deep sequencing. We extended our methodology to map multiple specificities of epitopes targeted in polyclonal sera, elicited in immunized animals as well as in HIV-1 infected patients.


title: Kinetic control of MERS-CoV 3CLpro is mediated by non-conserved residues distal to the active site

text: Middle-East Respiratory Syndrome (MERS) Coronavirus is a re-emergent zoonotic pathogen with a 30% fatality rate in humans The MERS positive-sense single-stranded RNA genome is translated into two polyproteins that must be processed by two viral cysteine proteases (3CLpro and PLpro) into 16 non-structural proteins (nsp) before viral replication can occur Attempts to drug either of these cysteine proteases have proven difficult MERS 3CLpro functions as dimer and is unique among all of the coronavirus 3CLpro enzymes studied to date because competitive inhibitors activate the wild-type MERS 3CLpro enzyme at low inhibitor concentrations and inhibit at higher concentrations This mechanism of substrate/inhibitor-induced dimerization seems to be mediated by non-conserved residues in structural regions distal to the catalytic site We have identified unique residues that are involved in the inhibitor-induced dimerization mechanism and we show that these ?competitive? inhibitors activate and inhibit in a dose-dependent manner In an attempt to provide a structural basis for this mechanism, we crystallized the apo and inhibitor-bound forms of this enzyme and diffracted them to 1 5 ? 2 2 Å We also show that residues in distinct structural regions synergize to modulate the intrinsic kinetic parameters of this family of enzymes These parameters include increased turnover (kcat) and a lower dimer dissociation constant (KD) Additionally, a rapid-equilibrium kinetic mechanism was developed to model the kinetic response of MERS 3CLpro to inhibitors that act via substrate/inhibitor induced activation/inhibition mechanisms Support or Funding Information This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contracts No HHSN272200700058C, HHSN272201200026C, and HHSN272201700060C This research used resources of the Advanced Photon Source, a U S Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No DE-AC02-06CH11357 Use of the Lilly Research Laboratories Collaborative Access Team (LRL-CAT) beamline at Sector 31 of the Advanced Photon Source was provided by Eli Lilly Company, which operates the facility


title: Predicting Mortality Risk in Patients with COVID-19 Using Artificial Intelligence to Help Medical Decision-Making

text: In the wake of COVID-19 disease, caused by the SARS-CoV-2 virus, we designed and developed a predictive model based on Artificial Intelligence (AI) and Machine Learning algorithms to determine the health risk and predict the mortality risk of patients with COVID-19. In this study, we used documented data of 117,000 patients world-wide with laboratory-confirmed COVID-19. This study proposes an AI model to help hospitals and medical facilities decide who needs to get attention first, who has higher priority to be hospitalized, triage patients when the system is overwhelmed by overcrowding, and eliminate delays in providing the necessary care. The results demonstrate 93% overall accuracy in predicting the mortality rate. We used several machine learning algorithms including Support Vector Machine (SVM), Artificial Neural Networks, Random Forest, Decision Tree, Logistic Regression, and K-Nearest Neighbor (KNN) to predict the mortality rate in patients with COVID-19. In this study, the most alarming symptoms and features were also identified. Finally, we used a separate dataset of COVID-19 patients to evaluate our developed model accuracy, and used confusion matrix to make an in-depth analysis of our classifiers and calculate the sensitivity and specificity of our model.


title: Automated and partially-automated contact tracing: a rapid systematic review to inform the control of COVID-19

text: Background Automated or partially-automated contact tracing tools are being deployed by many countries to contain SARS-CoV-2; however, the evidence base for their use is not well-established. Methods We undertook a rapid systematic review of automated or partially-automated contact tracing, registered with PROSPERO (CRD42020179822). We searched PubMed, EMBASE, OVID Global Health, EBSCO COVID Portal, Cochrane Library, medRxiv, bioRxiv, arXiv and Google Advanced for articles relevant to COVID-19, SARS, MERS, influenza or Ebola from 1/1/2000-14/4/2020. Two authors reviewed all full-text manuscripts. One reviewer extracted data using a pre-piloted form; a second independently verified extracted data. Primary outcomes were the number or proportion of contacts (and/or subsequent cases) identified; secondary outcomes were indicators of outbreak control, app/tool uptake, resource use, cost-effectiveness and lessons learnt. The Effective Public Health Practice Project tool or CHEERS checklist were used in quality assessment. Findings 4,033 citations were identified and 15 were included. No empirical evidence of automated contact tracing's effectiveness (regarding contacts identified or transmission reduction) was identified. Four of seven included modelling studies suggested that controlling COVID-19 requires high population uptake of automated contact-tracing apps (estimates from 56% to 95%), typically alongside other control measures. Studies of partially-automated contact tracing generally reported more complete contact identification and follow-up, and greater intervention timeliness (0.5-5 hours faster), than previous systems. No meta-analyses were possible. Interpretation Automated contact tracing has potential to reduce transmission with sufficient population uptake and usage. However, there is an urgent need for well-designed prospective evaluations as no studies provided empirical evidence of its effectiveness.


title: Improved deep learning model for differentiating novel coronavirus pneumonia and influenza pneumonia

text: Background: Chest CT had high sensitivity in diagnosing novel coronavirus pneumonia (NCP) at early stage, giving it an advantage over nucleic acid detection in time of crisis. Deep learning was reported to discover intricate structures from clinical images and achieve expert-level performance in medical image analysis. To develop and validate an integrated deep learning framework on chest CT images for auto-detection of NCP, particularly focusing on differentiating NCP from influenza pneumonia (IP). Methods: 35 confirmed NCP cases were consecutively enrolled as training set from 1138 suspected patients in three NCP designated hospitals together with 361 confirmed viral pneumonia patients from center one including 156 IP patients, from May, 2015 to February, 2020. The external validation set enrolled 57 NCP patients and 50 IP patients from eight centers. Results: 96.6% of NCP lesions were larger than 1 cm and 76.8% were with intensity below -500 Hu, indicating less consolidation than IP lesions which had nodules ranging 5-10 mm. The classification schemes accurately distinguished NCP and IP lesions with area under the receiver operating characteristic curve (AUC) above 0.93. The Trinary scheme was more device-independent and consistent with specialists than the Plain scheme, which achieved a F1 score of 0.847, higher than the Plain scheme (0.774), specialists (0.785) and residents (0.644). Conclusions: Our study potentially provides an accurate early diagnosis tool on chest CT for NCP with high transferability, and shows high efficiency in differentiating NCP and IP, helping to reduce misdiagnosis and contain the pandemic transmission.


title: An application of Delphi method and analytic hierarchy process in understanding hotel corporate social responsibility performance scale

text: This study aims to identify the essential indicators of hotel Corporate Social Responsibility (CSR) performance measurement with a standardized and composite CSR performance measurement index for the hotel industry. Employing both Delphi and Analytic Hierarchy Process (AHP) methods, three stakeholder groups are surveyed: academicians; hotel managers; and, hotel customers. Results reveal that three traditional CSR domains (legal, ethical, and social/philanthropic) are primary contributors to CSR performance, followed by two new environmental domains (room and restaurant; other general areas), and financial/economic domains as secondary contributors. This study shows the high level of consistency in the responses from stakeholder groups, supporting the effectiveness of the scale as a valuable tool to measure hotel CSR performance. Notably, domain weighted scores do differ slightly by respondent characteristic, indicating that the impacts of CSR are sensitive to respondent diversity.


Embolia pulmonar aguda durante la cuarentena por COVID-19


title: Early outcomes of tocilizumab in adults hospitalized with severe COVID19. An initial report from the Vall dHebron COVID19 prospective cohort study.

text: Background: Modulation of the immune system to prevent lung injury is being widely used against the new coronavirus disease (COVID19) despite the scarcity of evidence. Methods: We report preliminary results from the Vall dHebron prospective cohort study at Vall dHebron University Hospital, in Barcelona (Spain), including all consecutive patients who had a confirmed infection with the severe acute respiratory syndrome coronavirus2 (SARSCoV2) and who were treated with tocilizumab until March 25th. The primary endpoint was mortality at 7 days after tocilizumab administration. Secondary endpoints were admission to the intensive care unit, development of ARDS and respiratory insufficiency among others. Results: 82 patients with COVID19 received at least one dose of tocilizumab. The mean (SD) age was 59.1 (19.8) years, 63% were male, 22% were of non Spanish ancestry, and the median (IQR) ageadjusted Charlson index at baseline was 3 (1 to 4) points. Respiratory failure and ARDS developed in 62 (75.6%) and 45 (54.9%) patients, respectively. Median time from symptom onset to ARDS development was 8 (5 to 11) days. The median time from symptom onset to the first dose of tocilizumab was 9 (7 to 11) days. Mortality at 7 days was 26.8%. Hazard ratio for mortality was 3.3; 95% CI, 1.3 to 8.5 (age adjusted hazard ratio for mortality 2.1; 95% CI, 0.8 to 5.8) if tocilizumab was administered after the onset of ARDS. Conclusion: Time from lung injury onset to tocilizumab administration may be critical to patient recovery. Our preliminary data could inform bedside decisions until more data from clinical trials becomes available.


docid: irtdqbeb

title: The long term predictions from Imperial College CovidSim Report 9

text: We present calculations using the CovidSim code which implements the Imperial College individual-based model of the COVID epidemic. Using the parameterization assumed in March 2020, we reproduce the predictions presented to inform UK government policy in March 2020. We find that CovidSim would have given a good forecast of the subsequent data if a higher initial value of R0 had been assumed. We then investigate further the whole trajectory of the epidemic, presenting results not previously published. We find that while prompt interventions are highly effective at reducing peak ICU demand, none of the pro- posed mitigation strategies reduces the predicted total number of deaths below 200,000. Surprisingly, some interventions such as school closures were predicted to increase the projected total number of deaths.


title: Conspiracy beliefs are associated with lower knowledge and higher anxiety levels regarding COVID-19 among students at the University of Jordan

text: Background: The world has been afflicted heavily by the burden of coronavirus disease 2019 (COVID-19) that overwhelmed health care systems and caused severe economic and educational deficits, in addition to anxiety among the public. The main aim of this study was to evaluate the mutual effects of belief that the pandemic was the result of a global conspiracy on knowledge and anxiety levels among students at the University of Jordan (UJ). Methods: An electronic-based survey was conducted between March 29th 2020 and March 31st 2020. The targeted population involved all undergraduate and postgraduate students from Health, Scientific and Humanities Schools at UJ. Survey sections included 26 items on: socio-demographic information, knowledge and sources of information about the disease, attitude towards the false notion that COVID-19 stemmed from a global conspiracy and items to assess the anxiety level among students during the quarantine period. Results: The total number of participants was 1540 students. The majority of participants perceived the disease as moderately dangerous (n=1079, 70.1%), with males, Jordanians and participants with lower income being more inclined to feel that the disease is very dangerous (p<0.001, 0.020, and <0.001, respectively). Lower level of knowledge and higher level of anxiety about COVID-19 were associated with the belief that the disease is part of a global conspiracy (p<0.001 and p=0.004, respectively). Females and participants with lower income were more likely to believe that the disease is related to conspiracy (p=0.001 and p<0.001, respectively). Belief in global conspiracy regarding the origin of COVID-19 was associated with misinformation about the availability of vaccine and the therapeutic use of antibiotics for COVID-19 treatment (p=0.001 and p<0.001, respectively). Ministry of Health in Jordan was the most common source of information about COVID-19 reported by the participants (n=1018). Conclusions: The false belief that COVID-19 was the result of a global conspiracy could be the consequence of lower level of knowledge about the virus and could lead to higher level of anxiety, which should be considered in the awareness tools of various media platforms about the current pandemic.


docid: iuvqrjau

title: Banishing Gradgrind's Ghost: A Book Review HOW WE TEACH SCIENCE: WHAT'S CHANGED, AND WHY IT MATTERS John L. Rudolph's (Cambridge, MA: Harvard University Press, 2019, 308 pages, ISBN 978067491341, $35.00)


title: Mapping Systemic Inflammation and Antibody Responses in Multisystem Inflammatory Syndrome in Children (MIS-C)

text: Initially, the global outbreak of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spared children from severe disease. However, after the initial wave of infections, clusters of a novel hyperinflammatory disease have been reported in regions with ongoing SARS-CoV-2 epidemics. While the characteristic clinical features are becoming clear, the pathophysiology remains unknown. Herein, we report on the immune profiles of eight Multisystem Inflammatory Syndrome in Children (MIS-C) cases. We document that all MIS-C patients had evidence of prior SARS-CoV-2 exposure, mounting an antibody response with normal isotype-switching and neutralization capability. We further profiled the secreted immune response by high-dimensional cytokine assays, which identified elevated signatures of inflammation (IL-18 and IL-6), lymphocytic and myeloid chemotaxis and activation (CCL3, CCL4, and CDCP1) and mucosal immune dysregulation (IL-17A, CCL20, CCL28). Mass cytometry immunophenotyping of peripheral blood revealed reductions of mDC1 and non-classical monocytes, as well as both NK- and T- lymphocytes, suggesting extravasation to affected tissues. Markers of activated myeloid function were also evident, including upregulation of ICAM1 and FcR1 in neutrophil and non-classical monocytes, well-documented markers in autoinflammation and autoimmunity that indicate enhanced antigen presentation and Fc-mediated responses. Finally, to assess the role for autoimmunity secondary to infection, we profiled the auto-antigen reactivity of MIS-C plasma, which revealed both known disease-associated autoantibodies (anti-La) and novel candidates that recognize endothelial, gastrointestinal and immune-cell antigens. All patients were treated with anti- IL6R antibody or IVIG, which led to rapid disease resolution tracking with normalization of inflammatory markers.


title: The COVID-19 Critical Care Consortium observational study: Design and rationale of a prospective, international, multicenter, observational study

text: Importance: There is a paucity of data that can be used to guide the management of critically ill patients with coronavirus disease 2019 (COVID-19). Global collaboration offers the best chance of obtaining these data, at scale and in time. In the absence of effective therapies, insights derived from real-time observational data will be a crucial means of improving outcomes. Objective: In response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, a research and data-sharing collaborative has been assembled to harness the cumulative experience of intensive care units (ICUs) worldwide. The resulting observational study provides a platform to rapidly disseminate detailed data and insights. Design: The COVID-19 Critical Care Consortium observational study is an international, multicenter, prospective, observational study of patients with confirmed or suspected SARS-CoV-2 infection admitted to ICUs. Setting: This is an evolving, open-ended study that commenced on January 1st, 2020 and currently includes more than 350 sites in over 48 countries. The study enrolls patients at the time of ICU admission and follows them to the time of death, hospital discharge, or 28 days post-ICU admission, whichever occurs last. Participants: All subjects, without age limit, requiring admission to an ICU for SARS-CoV-2 infection, confirmed by real-time polymerase chain reaction (PCR) and/or next-generation sequencing or with high clinical suspicion of the infection. Patients admitted to an ICU for any other reason are excluded. Main outcomes and measures: Key data, collected via an electronic case report form devised in collaboration with the ISARIC/SPRINT-SARI networks, include: patient demographic data and risk factors, clinical features, severity of illness and respiratory failure, need for non-invasive and/or mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO), and associated complications, as well as data on adjunctive therapies. Final outcomes of in-hospital death, discharge or continuing admissions at 28 days. Discussion: This large-scale, observational study of COVID-19 in the critically ill will provide rapid international characterization. Open-ended accrual will increase the power to answer hypothesis-led questions over time. Several sub-studies have already been initiated, examining hemostasis, neurological, cardiac, and long-term outcomes.


title: Inhaled corticosteroid use and risk COVID-19 related death among 966,461 patients with COPD or asthma: an OpenSAFELY analysis

text: Background: Early descriptions of the coronavirus outbreak showed a lower prevalence of asthma and COPD than was expected for people diagnosed with COVID-19, leading to speculation that inhaled corticosteroids (ICS) may protect against infection with SARS-CoV-2, and development of serious sequelae. We evaluated the association between ICS and COVID-19 related death using linked electronic health records in the UK. Methods: We conducted cohort studies on two groups of people (COPD and asthma) using the OpenSAFELY platform to analyse data from primary care practices linked to national death registrations. People receiving an ICS were compared to those receiving alternative respiratory medications. Our primary outcome was COVID-19 related death. Findings: We identified 148,588 people with COPD and 817,973 people with asthma receiving relevant respiratory medications in the four months prior to 01 March 2020. People with COPD receiving ICS were at a greater risk of COVID-19 related death compared to those receiving a long-acting beta agonist (LABA) and a long-acting muscarinic antagonist (LAMA) (adjusted HR = 1.38, 95% CI = 1.08 - 1.75). People with asthma receiving high dose ICS were at an increased risk of death compared to those receiving a short-acting beta agonist (SABA) only (adjusted HR = 1.52, 95%CI = 1.08 - 2.14); the adjusted HR for those receiving low-medium dose ICS was 1.10 (95% CI = 0.82 - 1.49). Quantitative bias analyses indicated that an unmeasured confounder of only moderate strength of association with exposure and outcome could explain the observed associations in both populations. Interpretation: These results do not support a major role of ICS in protecting against COVID-19 related deaths. Observed increased risks of COVID-19 related death among people with COPD and asthma receiving ICS can be plausibly explained by unmeasured confounding due to disease severity.


title: Causal empirical estimates suggest COVID-19 transmission rates are highly seasonal

text: Nearly every country is now combating the 2019 novel coronavirus (COVID-19). It has been hypothesized that if COVID-19 exhibits seasonality, changing temperatures in the coming months will shift transmission patterns around the world. Such projections, however, require an estimate of the relationship between COVID-19 and temperature at a global scale, and one that isolates the role of temperature from confounding factors, such as public health capacity. This paper provides the first plausibly causal estimates of the relationship between COVID-19 transmission and local temperature using a global sample comprising of 166,686 confirmed new COVID-19 cases from 134 countries from January 22, 2020 to March 15, 2020. We find robust statistical evidence that a 1°C increase in local temperature reduces transmission by 13% [-21%, -4%, 95%CI]. In contrast, we do not find that specific humidity or precipitation influence transmission. Our statistical approach separates effects of climate variation on COVID-19 transmission from other potentially correlated factors, such as differences in public health responses across countries and heterogeneous population densities. Using constructions of expected seasonal temperatures, we project that changing temperatures between March 2020 and July 2020 will cause COVID-19 transmission to fall by 43% on average for Northern Hemisphere countries and to rise by 71% on average for Southern Hemisphere countries. However, these patterns reverse as the boreal winter approaches, with seasonal temperatures in January 2021 increasing average COVID-19 transmission by 59% relative to March 2020 in northern countries and lowering transmission by 2% in southern countries. These findings suggest that Southern Hemisphere countries should expect greater transmission in the coming months. Moreover, Northern Hemisphere countries face a crucial window of opportunity: if contagion-containing policy interventions can dramatically reduce COVID-19 cases with the aid of the approaching warmer months, it may be possible to avoid a second wave of COVID-19 next winter.


title: India’s push to relax environmental assessment rules amid pandemic draws criticism

text: Environmentalists in India are criticizing government moves to continue to approve major industrial projects, and to relax the nation’s environmental assessment rules, even as the COVID-19 pandemic has complicated public oversight and canceled potential field reviews “They are carrying on as if there is no health emergency, hosting meetings and taking decisions including on big ticket projects,” said Kanchi Kohli, an environmental governance expert with the Centre for Policy Research “Public engagement, ground verification—these options are all foreclosed at this time ”


title: Efficacy of face mask in preventing respiratory virus transmission: a systematic review and meta-analysis

text: Background: Conflicting recommendations exist related to whether masks have a protective effect on the spread of respiratory viruses. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was consulted to report this systematic review. Relevant articles were retrieved from PubMed, Web of Science, ScienceDirect, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI), VIP (Chinese) database. Results: A total of 21 studies met our inclusion criteria. Meta-analyses suggest that mask use provided a significant protective effect (OR = 0.35 and 95% CI = 0.24-0.51). Use of masks by healthcare workers (HCWs) and non-healthcare workers (Non-HCWs) can reduce the risk of respiratory virus infection by 80% (OR = 0.20, 95% CI = 0.11-0.37) and 47% (OR = 0.53, 95% CI = 0.36-0.79). The protective effect of wearing masks in Asia (OR = 0.31) appeared to be higher than that of Western countries (OR = 0.45). Masks had a protective effect against influenza viruses (OR = 0.55), SARS (OR = 0.26), and SARS-CoV-2 (OR = 0.04). In the subgroups based on different study designs, protective effects of wearing mask were significant in cluster randomized trials, case-control studies and retrospective studies. Conclusions: This study adds additional evidence of the enhanced protective value of masks, we stress that the use masks serve as an adjunctive method regarding the COVID-19 outbreak.


title: Estimating the scale of COVID-19 Epidemic in the United States: Simulations Based on Air Traffic directly from Wuhan, China

text: Introduction: Coronavirus Disease 2019 (COVID-19) infection has been characterized by rapid spread and unusually large case clusters. It is important to have an estimate of the current state of COVID-19 epidemic in the U.S. to develop informed public health strategies. Methods: We estimated the potential scale of the COVID-19 epidemic (as of 03/01/2020) in the U.S. from cases imported directly from Wuhan area. We used simulations based on transmission dynamics parameters estimated from previous studies and air traffic data from Wuhan to the U.S and deliberately built our model based on conservative assumptions. Detection and quarantine of individual COVID-19 cases in the U.S before 03/01/2020 were also taken into account. We. A SEIR model was used to simulate the growth of the number of infected individuals in Wuhan area and in the U.S. Results: With the most likely model, we estimated that there would be 9,484 infected cases (90%CI 2,054-24,241) as of 03/01/2020 if no intervention procedure had been taken to reduce the transmissibility in unidentified cases. Assuming current preventive procedures have reduced 25% of the transmissibility in unidentified cases, the number of infected cases would be 1,043 (90%CI 107-2,474). Conclusion: Our research indicates that, as of 03/01/2020., it is likely that there are already thousands of individuals in the US infected with SARS-CoV-2. Our model is dynamic and is available to the research community to further evaluate as the situation becomes clearer.


First Person: Administrator to COVID-19 Staff: We're Not Making Enough MoneyBreaking News: Death Is an Expected COVID-19 Effect;Covidlateral Damage Is Not


title: Single-cell RNA Analysis on ACE2 Expression Provides Insight into SARS-CoV-2 Blood Entry and Heart Injury

text: COVID-19 is a global pandemic with high infectivity and pathogenicity, accounting for tens of thousands of deaths worldwide. Recent studies have found that the pathogen of COVID-19, SARS-CoV-2, shares the same cell receptor Angiotensin converting enzyme II (ACE2) with SARS-CoV. The pathological investigation of COVID-19 death showed that the lung had the characteristics of pulmonary fibrosis. However, how SARS-CoV-2 spreads from the lungs to other organs has not yet been determined. Here, we performed an unbiased evaluation of cell-type specific expression of ACE2 in healthy and fibrotic lungs, as well as in normal and failed adult human hearts, using published single-cell RNA-seq data. We found that ACE2 expression in fibrotic lungs mainly locates in arterial vascular cells, which might provide the route for bloodstream spreading of SARS-CoV-2. The failed human hearts have a higher percentage of ACE2-expressing cardiomyocytes, and SARS-CoV-2 might attack cardiomyocytes through the bloodstream in patients with heart failure. Moreover, ACE2 was highly expressed in cells infected by RSV or MERS-CoV and in mice treated by LPS. Our findings indicate that patients with pulmonary fibrosis, heart failure, and virus infection have a higher risk and are more susceptible to SARS-CoV-2 infection. SARS-CoV-2 might attack other organs by getting into the bloodstream. This work provides new insights into SARS-CoV-2 blood entry and heart injury and might propose a therapeutic strategy to prevent patients from developing severe complications.


title: Intrinsic growth rules of patients infected, dead and recovered with 2019 novel coronavirus in mainland China

text: An outbreak of a novel coronavirus (SARS-CoV-2)-infected pneumonia (COVID-19) was first diagnosed in Wuhan, China, in December 2019 and then spread rapidly to other regions. We collected the time series data of the cumulative number of confirmed infected, dead, and cured cases from the health commissions in 31 provinces in mainland China. A descriptive model in a logistic form was formulated to infer the intrinsic epidemic rules of COVID-19, which illustrates robustness spatially and temporally. Our model is robust (R2>0.95) to depict the intrinsic growth rule for the cumulative number of confirmed infected, dead, and cured cases in 31 provinces in mainland China. Furthermore, we compared the intrinsic epidemic rules of COVID-19 in Hubei with that of severe acute respiratory syndrome (SARS) in Beijing, which was obtained from the Ministry of Public Health of China in 2003. We found that the infected case is the earliest to be saturated and has the lowest semi-saturation period compared with deaths and cured cases for both COVID-19 and SARS. All the three types of SARS cases are later to saturate and have longer semi-saturation period than that of COVID-19. Despite the virus caused SARS (SARS-CoV) and the virus caused COVID-19 (SARS-CoV-2) are homologous, the duration of the outbreak would be shorter for COVID-19.


title: Can United States intelligence community analysts telework?

text: This article argues that United States Intelligence Community analysts can and should periodically telework as routine professional development and as a research supplement to traditional all-source intelligence analysis. We offer four key benefits to tapping into this reservoir of unclassified information that would improve the quality of the intelligence product, enable better liaison and academic exchange, and steward the profession. We conclude that an overdue rebalancing of classified and publicly available sources could be aided by telework, but only once analysts break free from ‘the cult of the SCIF’ will publicly available information receive the analytical attention that it deserves.


Development of a COVID-19 Point-of-Care Ultrasound (POCUS) Protocol


docid: iinpkixn

title: Anti-frameshifting ligand active against SARS coronavirus-2 is resistant to natural mutations of the frameshift-stimulatory pseudoknot

text: The coronavirus SARS-CoV-2 causing the COVID-19 pandemic uses −1 programmed ribosomal frameshifting (−1 PRF) to control the expression levels of key viral proteins. Because modulating −1 PRF can attenuate viral propagation, ligands binding to the viral RNA pseudoknot that stimulates −1 PRF may prove useful as therapeutics. Mutations in the pseudoknot have been observed over the course of the pandemic, but how they affect −1 PRF and the activity of inhibitors is unknown. Cataloguing natural mutations in all parts of the SARS-CoV-2 pseudoknot, we studied a panel of 6 mutations in key structural regions. Most mutations left the −1 PRF efficiency unchanged, even when base-pairing was disrupted, but one led to a remarkable three-fold decrease, suggesting that SARS-CoV-2 propagation may be less sensitive to modulation of −1 PRF efficiency than some other viruses. Examining the effects of one of the few small-molecule ligands known to suppress −1 PRF significantly in SARS-CoV, we found that it did so by similar amounts in all SARS-CoV-2 mutants tested, regardless of the basal −1 PRF efficiency, indicating that the activity of anti-frameshifting ligands can be resistant to natural pseudoknot mutations. These results have important implications for therapeutic strategies targeting SARS-CoV-2 through modulation of −1 PRF.


title: Optimal Allocation of COVID-19 Test Kits Among Accredited Testing Centers in the Philippines

text: Testing is crucial for early detection, isolation, and treatment of coronavirus disease (COVID-19)-infected individuals. However, in resource-constrained countries such as the Philippines, test kits have limited availability. As of 12 April 2020, there are 11 testing centers in the country that have been accredited by the Department of Health (DOH) to conduct testing. In this paper, we determine the optimal percentage allocation of COVID-19 test kits among accredited testing centers in the Philippines that gives an equitable chance to all infected individuals to be tested. Heterogeneity in testing accessibility, population density of municipalities, and the capacity of testing facilities are included in the model. Our results showed that the range of optimal allocation per testing center are: Research Institute for Tropical Medicine (4.17%-6.34%), San Lazaro Hospital (14.65%-24.03%), University of the Philippines-National Institutes of Health (16.25%-44.80%), Lung Center of the Philippines (15.8%-26.40%), Baguio General Hospital Medical Center (0.58%-0.76%), The Medical City, Pasig City (5.96%-25.51%), St. Luke's Medical Center, Quezon City (1.09%-6.70%), Bicol Public Health Laboratory (0.06%-0.08%), Western Visayas Medical Center (0.71%-4.52%), Vicente Sotto Memorial Medical Center (1.02%-2.61%), and Southern Philippines Medical Center (approx 0.01%). If there will be changes in the number of testing centers, our model can still be used to modify the test kit allocation. Our results can serve as a guide to the authorities in distributing the COVID-19 test kits. These can also be used to determine the capacity of testing centers and the effects of increasing its number. The model can also be used for proposing additional number and location of new testing centers.


title: COVID-19 and treatment with NSAIDs and corticosteroids: should we be limiting their use in the clinical setting?

text: Given the current SARS-CoV-2 (COVID-19) pandemic, the availability of reliable information for clinicians and patients is paramount. There have been a number of reports stating that non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids may exacerbate symptoms in COVID-19 patients. Therefore, this review aimed to collate information available in published articles to identify any evidence behind these claims with the aim of advising clinicians on how best to treat patients. This review found no published evidence for or against the use of NSAIDs in COVID-19 patients. Meanwhile, there appeared to be some evidence that corticosteroids may be beneficial if utilised in the early acute phase of infection, however, conflicting evidence from the World Health Organisation surrounding corticosteroid use in certain viral infections means this evidence is not conclusive. Given the current availability of literature, caution should be exercised until further evidence emerges surrounding the use of NSAIDs and corticosteroids in COVID-19 patients.


docid: auasueaw

title: Semiparametric Relative-risk Regression for Infectious Disease Data

text: This paper introduces semiparametric relative-risk regression models for infectious disease data based on contact intervals, where the contact interval from person i to person j is the time between the onset of infectiousness in i and infectious contact from i to j. The hazard of infectious contact from i to j is \lambda_0(\tau)r(\beta_0^T X_{ij}), where \lambda_0(\tau) is an unspecified baseline hazard function, r is a relative risk function, \beta_0 is an unknown covariate vector, and X_{ij} is a covariate vector. When who-infects-whom is observed, the Cox partial likelihood is a profile likelihood for \beta maximized over all possible \lambda_0(\tau). When who-infects-whom is not observed, we use an EM algorithm to maximize the profile likelihood for \beta integrated over all possible combinations of who-infected-whom. This extends the most important class of regression models in survival analysis to infectious disease epidemiology.


title: Lack of Reinfection in Rhesus Macaques Infected with SARS-CoV-2

text: A global pandemic of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is ongoing spread. It remains unclear whether the convalescing patients have a risk of reinfection. Rhesus macaques were rechallenged with SARS-CoV-2 during an early recovery phase from initial infection characterized by weight loss, interstitial pneumonia and systemic viral dissemination mainly in respiratory and gastrointestinal tracts. The monkeys rechallenged with the identical SARS-CoV-2 strain have failed to produce detectable viral dissemination, clinical manifestations and histopathological changes. A notably enhanced neutralizing antibody response might contribute the protection of rhesus macaques from the reinfection by SARS-CoV-2. Our results indicated that primary SARS-CoV-2 infection protects from subsequent reinfection. One Sentence Summary Neutralizing antibodies against SARS-CoV-2 might protect rhesus macaques which have undergone an initial infection from reinfection during early recovery days.


title: No evidence for allelic association between Covid-19 and ACE2 genetic variants by direct exome sequencing in 99 SARS-CoV-2 positive patients

text: Background: Coronaviruses (CoV) are a large family of viruses that are common in people and many animal species. Animal coronaviruses rarely infect humans with the exceptions of the Middle East Respiratory Syndrome (MERS-CoV), the Severe acute respiratory syndrome coronavirus (SARS-CoV), and now SARS-CoV-2, which is the cause of the ongoing pandemic of coronavirus disease 2019 (COVID-19). Many studies suggested that genetic variants in ACE2 gene may influence the host susceptibility/resistance to SARS-CoV-2 virus according to the functional role of ACE2 in human pathophysiology. However, all these studies have been conducted in silico based on epidemiological and population data. We therefore investigated the occurrence of ACE2 variants in a cohort of 99 Italian unrelated individuals clinically diagnosed with coronavirus disease 19 (COVID-19) to experimental demonstrate allelic association with disease severity. Methods: By whole-exome sequencing we analysed 99 DNA samples of severely and extremely severely COVID-19 patients hospitalized at the University Hospital of Rome Tor Vergata and Bambino Gesu Hospital in Rome. Results: We identified three different germline variants, one intronic (c.439+4G>A) and two missense (c.2158A>G, p.Asn720Asp; c.1888G>C, p.Asp630His ), in 26 patients with a similar frequency between male and female and a not statistically different frequency, except for c.1888G>C, (p.Asp630His) with the ethnically matched populations (EUR). Conclusions: Our results suggest that there is not any ACE2 exonic allelic association with disease severity. It is possible that rare susceptibility alleles are located in the non-coding region of the gene able to control ACE2 gene activity. It is therefore of interest, to explore the existence of ACE2 susceptibility alleles to SARS-Co-V2 in these regulatory regions. In addition, we found no significant evidence that ACE2 alleles is associated with disease severity/sex bias in the Italian population.


title: Type I and Type III IFN Restrict SARS-CoV-2 Infection of Human Airway Epithelial Cultures

text: The newly emerged human coronavirus, SARS-CoV-2, has caused a pandemic of respiratory illness. The innate immune response is critical for protection against Coronaviruses. However, little is known about the interplay between the innate immune system and SARS-CoV-2. Here, we modeled SARS-CoV-2 infection using primary human airway epithelial (pHAE) cultures, which are maintained in an air-liquid interface. We found that SARS-CoV-2 infects and replicates in pHAE cultures and is directionally released on the apical, but not basolateral surface. Transcriptional profiling studies found that infected pHAE cultures had a molecular signature dominated by pro-inflammatory cytokines and chemokine induction, including IL-6, TNFα, CXCL8. We also identified NF-κB and ATF4 transcription factors as key drivers of this pro-inflammatory cytokine response. Surprisingly, we observed a complete lack of a type I or III IFN induction during SARS-CoV-2 infection. Pre-treatment or post-treatment with type I and III IFNs dramatically reduced virus replication in pHAE cultures and this corresponded with an upregulation of antiviral effector genes. Our findings demonstrate that SARS-CoV-2 induces a strong pro-inflammatory cytokine response yet blocks the production of type I and III IFNs. Further, SARS-CoV-2 is sensitive to the effects of type I and III IFNs, demonstrating their potential utility as therapeutic options to treat COVID-19 patients. IMPORTANCE The current pandemic of respiratory illness, COVID-19, is caused by a recently emerged coronavirus named SARS-CoV-2. This virus infects airway and lung cells causing fever, dry cough, and shortness of breath. Severe cases of COVID-19 can result in lung damage, low blood oxygen levels, and even death. As there are currently no vaccines or antivirals approved for use in humans, studies of the mechanisms of SARS-CoV-2 infection are urgently needed. SARS-CoV-2 infection of primary human airway epithelial cultures induces a strong pro-inflammatory cytokine response yet blocks the production of type I and III IFNs. Further, SARS-CoV-2 is sensitive to the effects of type I and III IFNs, demonstrating their potential utility as therapeutic options to treat COVID-19 patients.


title: A Computational Toolset for Rapid Identification of SARS-CoV-2, other Viruses, and Microorganisms from Sequencing Data

text: In this paper, we present a toolset and related resources for rapid identification of viruses and microorganisms from short-read or long-read sequencing data. We present fastv as an ultra-fast tool to detect microbial sequences present in sequencing data, identify target microorganisms, and visualize coverage of microbial genomes. This tool is based on the k-mer mapping and extension method. K-mer sets are generated by UniqueKMER, another tool provided in this toolset. UniqueKMER can generate complete sets of unique k-mers for each genome within a large set of viral or microbial genomes. For convenience, unique k-mers for microorganisms and common viruses that afflict humans have been generated and are provided with the tools. As a lightweight tool, fastv accepts FASTQ data as input, and directly outputs the results in both HTML and JSON formats. Prior to the k-mer analysis, fastv automatically performs adapter trimming, quality pruning, base correction, and other pre-processing to ensure the accuracy of k-mer analysis. Specifically, fastv provides built-in support for rapid SARS-CoV-2 identification and typing. Experimental results showed that fastv achieved 100% sensitivity and 100% specificity for detecting SARS-CoV-2 from sequencing data; and can distinguish SARS-CoV-2 from SARS, MERS, and other coronaviruses. This toolset is available at: https://github.com/OpenGene/fastv.


title: Economic crisis as a consequence COVID-19 virus attack: risk and damage assessment

text: The purpose of the research is to reveal the mechanism of influence of coronavirus on the economic crisis and to develop a method for assessing threats and risks Understanding the mechanism of generating an economic crisis allows to develop methods of anti-crisis government policy The research methodology is based on structural analysis and taxonomic approach Their application makes it possible to distinguish activities with decreasing demand relative to initial supply, and with increasing demand, which generates deficits of goods The results of the research at the theoretical level of analysis is the proposed method of assessing threats and risks from the spread of coronavirus, which allows the benefits of certain types of activities (pharmaceuticals and medicine), and consider the damage on other activities (tourism, transportation, education) The diagram of the ratio of benefits and losses from the spread of the virus attack allows to position different economies in different zones of the diagram, according to the reaction of a particular economy to the epidemic, with a different scale of influence Using such a chart, estimating the expected damage and expected benefits, the impact of COVID-19 on the economy is assessed based on changes in the dynamics of investments in financial and non-financial assets Analysis of financial and non-financial investments in some countries has led to the conclusion that the financial system that is less biased in terms of financial investment relative to the functioning of non-financial sectors is the least vulnerable in a crisis The multiple excess of financial investments over non-financial ones for Russia creates the foundation of financial instability and recession This is confirmed using econometric analysis and forecast Therefore, overcoming the economic crisis caused by COVID-19 in addition to the current measures will require correcting, in particular, the structure of "financial-non-financial" investments


title: Behavioral changes before lockdown, and decreased retail and recreation mobility during lockdown, contributed most to the successful control of the COVID-19 epidemic in 35 Western countries

text: The COVID-19 pandemic has prompted a lockdown in many countries to control the exponential spread of the SARS-CoV-2 virus. This resulted in curbing the epidemic by reducing the time-varying basic reproduction number (Rt) to below one. Governments are looking for evidence to balance the demand of their citizens to ease some of the restriction, against the fear of a second peak in infections. More details on the specific circumstances that promote exponential spread (i.e. Rt>1) and the measures that contributed most to a reduction in Rt are needed. Here we show that in 33 of 35 Western countries (32 European, plus Israel, USA and Canada), Rt fell to around or below one during lockdown (March - May 2020). One third of the effect happened already on average 6 days before the lockdown, with lockdown itself causing another major drop in transmission. Country-wide compulsory usage of masks was implemented only in Slovakia 10 days into lockdown, and on its own reduced transmission by half. During lockdown, decreased mobility in retail and recreation was an independent predictor of lower Rt during lockdown, while changes in other types of mobility were not. These results are consistent with anecdotal evidence that large recreational gatherings are super-spreading events, and may even suggest that infections during day-to-day contact at work are not sufficient to spark exponential growth. Our data suggest measures that will contribute to avoiding a second peak include a tight control on circumstances that facilitate massive spread such as large gatherings especially indoors, physical distancing, and mask use.


title: Type III interferons disrupt the lung epithelial barrier upon viral recognition

text: Lower respiratory tract infections are a leading cause of mortality driven by infectious agents. RNA viruses such as influenza virus, respiratory syncytial virus and the new pandemic coronavirus SARS-CoV-2 can be highly pathogenic. Clinical and experimental evidence indicate that most severe and lethal cases do not depend on the viral burden and are, instead, characterized by an aberrant immune response. In this work we assessed how the innate immune response contributes to the pathogenesis of RNA virus infections. We demonstrate that type III interferons produced by dendritic cells in the lung in response to viral recognition cause barrier damage and compromise the host tissue tolerance. In particular, type III interferons inhibit tissue repair and lung epithelial cell proliferation, causing susceptibility to lethal bacterial superinfections. Overall, our data give a strong mandate to rethink the pathophysiological roles of this group of interferons and their possible use in the clinical practice against endemic as well as emerging viral infections.


title: Gasless laparoscopy revisited in the SARS-CoV-2 pandemic

text: Reluctance towards general acceptance of gasless laparoscopic surgery has been mainly due to reservations on whether these techniques would create a greater extent of pain and surgical stress at the targeted site of abdominal wall lifting, and also whether the operating space achieved would be sufficient for the scope to be maneuvered effectively and safely in the abdominal cavity With the widespread mortality in patients infected by SARS-CoV-2, the most relevant gasless endoscopic techniques have been revisited to explore options in performing endoscopic procedures, especially in children with more safety by reducing aerosolized viral contamination


title: Correlating glycoforms of DC-SIGN with stability using a combination of enzymatic digestion and ion mobility MS

text: The immune scavenger protein DC-SIGN interacts with glycosylated proteins and has a putative role in facilitating viral infection. How these recognition events take place with different viruses is not clear and the effects of glycosylation on the folding and stability of DC-SIGN have not been reported. Here, we develop and apply a mass spectrometry-based approach to both uncover and characterise the effects of O-glycans on the stability of DC-SIGN. We first quantify the Core 1 & 2 O-glycan structures on the carbohydrate recognition and extracellular domains of the protein via sequential exoglycosidase sequencing. We then use ion mobility mass spectrometry to show how specific O-glycans, and/or single monosaccharide substitutions, alter both the overall collision cross section and the gas-phase stability of the glycoprotein isoforms of DC-SIGN. We find that rather than the mass or length of glycoprotein modifications, the stability of DC-SIGN is better correlated with the number of glycosylation sites. Collectively, our results exemplify a combined multi-dimensional MS approach, proficient in evaluating protein stability in response to both glycoprotein macro- and micro-heterogeneity and adding structural detail to the infection enhancer DC-SIGN.


title: COVID-19 (SARS-CoV-2) Ventilator Resource Management Using a Network Optimization Model and Predictive System Demand

text: The COVID-19 (SARS-CoV-2) pandemic is overwhelming global healthcare delivery systems due to the exponential spike in cases requiring specialty tests, facilities and equipment, including complex, precision devices like ventilators. In particular, the surge in critically ill patients has revealed a significant deficiency in regional availability of respiratory care ventilators. The authors offer a mathematical framework for ventilator distribution under scarcity conditions using an optimized network model and solver. The framework is interoperable with existing COVID-19 healthcare demand models and scales for different user-defined system sizes, including hospital networks, city, state, regional and national-scale prioritization. The authors' approach improves current capabilities for medical device resource management within the existing incident command system while accounting for availability of devices, ventilation treatment time periods, disinfection and cleaning between patients, as well as shipping logistics time. The authors present a proof of concept using a high fidelity COVID-19 data set from Colorado, discusses how to scale nationally, and emphasizes the importance of applying ethical human-in-the-loop decision making when using this or similar approaches to managing medical device resources during epidemic emergencies.


title: Immunity after COVID-19: protection or sensitization ?

text: Motivated by historical and present clinical observations, we discuss the possible unfavorable evolution of the immunity (similar to documented antibody-dependent enhancement scenarios) after a first infection with COVID-19. More precisely we ask the question of how the epidemic outcomes are affected if the initial infection does not provide immunity but rather sensitization to future challenges. We first provide background comparison with the 2003 SARS epidemic. Then we use a compartmental epidemic model structured by immunity level (taken here as age classes) that we fit on available data; this allows to derive quantitative insights into the future number of severe cases and deaths.


Endoscopia digestiva en tiempos de COVID-19: Resumen de recomendaciones/ Digestive endoscopy in an era of COVID-19


title: Staff testing for COVID-19 via an online pre-registration form

text: Background: Healthcare workers are at increased risk of contracting SARS-CoV-2 and potentially causing institutional outbreaks. Staff testing is critical in identifying and isolating infected individuals while also reducing unnecessary workforce depletion. Tygerberg Hospital implemented an online pre-registration system to expedite staff and cluster testing. Objectives: We aimed to identify (1) specific presentations associated with a positive or negative result for SARS-CoV-2 and (2) staff sectors where enhanced strategies for testing might be required. Methods: Retrospective descriptive study involving all clients making use of the hospital's pre-registration system during May 2020. Results: Of 799 clients, most were young and female with few comorbidities. The most common occupation was nurses followed by administrative staff, doctors and general assistants. Doctors tested earlier compared to other staff (median: 1.5 vs 4 days). The most frequent presenting symptoms were headache, sore throat, cough and myalgia. Amongst those testing positive (n=105), fever, altered smell, altered taste sensation, chills and history of fever were the most common symptoms. Three or more symptoms was more predictive of a positive test, but 12/145 asymptomatic clients also tested positive. Conclusion: Staff coronavirus testing using an online pre-registration form is a viable and acceptable strategy. While some presentations are less likely to be associated with SARS-CoV-2 infection, no symptom can completely exclude it. Staff testing should form part of a bundle of strategies to protect staff including wearing masks, regular hand washing, buddy screening, physical distancing, availability of PPE and special dispensation for COVID-19-related leave.


COVID‐19: Lessons from SARS and MERS


title: Extension and implementation of a system modelling the COVID-19 pandemic in Chile

text: We modelling the dynamics of the COVID-19 epidemic taking into account the role of the unreported cases. In a first section we extend the model recently introduced/ implemented by Liu, Magal, Seydi and Webb, by considering different transmission rates for the infectious and unreported states, and we couple three new states related to hospitalized and fatalities. In addition, we introduce an operator that incorporates the effects of mitigation measures at the different rates considered in the system. Finally, we implemented the extended model in the Chilean context by considering variable the transmission rates and the fraction of unreported cases, the latter through an argument that uses mortality rates. We conclude with several conclusions and lines of future research.


docid: bgfymxco

title: Exploring material basis and mechanism of Lianhua Qingwen Prescription against coronavirus based on network pharmacology/ 基于网络药理学的连花清瘟方抗冠状病毒的物质基础及机制探讨

text: Objective: To explore the active compounds and mechanism of Lianhua Qingwen Prescription for the treatment of coronavirus, and provide a reference for the treatment of COVID-19. Methods: With the help of TCMSP, Batman, Swiss Target Prediction and other databases, the chemical constituents and targets of Lianhua Qingwen Prescription were retrieved. Coronavirus disease targets were screened by GeneCards. Cytoscape software was used to construct a “drug-component-target-disease” interaction network map and potential target interactions, and the action mechanism was predicted through enrichment analysis. The main active ingredients of Lianhua Qingwen Prescription were verified by molecular docking with Mpro and ACE2. Results: A total of 100 active ingredients, 636 drug targets, and 347 disease targets were excavated, and 67 drug-disease common targets were obtained. The key targets involved PTGS2, IL6, CASP3, MAPK1, EGFR, ACE2, etc. A total of 1 946 entries were obtained by GO enrichment analysis, which mainly involved T cell activation, viral receptors, and inflammatory responses. KEGG pathway enrichment screened 166 signaling pathways, including renin-angiotensin system, Toll-like receptor signaling pathway, JAK-STAT signaling pathway, T cell receptor signaling pathway, TNF signaling pathway and so on. The molecular docking results showed that kaempferol, quercetin and luteolin had good binding ability with Mpro; And glycyrrhetinic acid, stigmasterol, indigo had good binding ability with ACE2. Conclusion: Lianhua Qingwen Prescription acts on coronavirus through multiple components, multiple targets, and multiple pathways. The main components have good binding ability with Mpro and ACE2, so as to have a therapeutic effect on COVID-19.


title: Epitope-Based Peptide Vaccine Against Severe Acute Respiratory Syndrome-Coronavirus-2 Nucleocapsid Protein: An in silico Approach

text: With an increasing fatality rate, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has emerged as a promising threat to human health worldwide. SARS-CoV-2 is a member of the Coronaviridae family, which is transmitted from animal to human and because of being contagious, further it transmitted human to human. Recently, the World Health Organization (WHO) has announced the infectious disease caused by SARS-CoV-2, which is known as coronavirus disease-2019 (COVID-2019) as a global pandemic. But, no specific medications are available for the treatment of COVID-19 so far. As a corollary, there is a need for a potential vaccine to impede the progression of the disease. Lately, it has been documented that the nucleocapsid (N) protein of SARS-CoV-2 is responsible for viral replication as well as interferes with host immune responses. We have comparatively analyzed the sequences of N protein of SARS-CoV-2 for the identification of core attributes and analyzed the ancestry through phylogenetic analysis. Subsequently, we have predicted the most immunogenic epitope for T-cell as well as B-cell. Importantly, our investigation mainly focused on major histocompatibility complex (MHC) class I potential peptides and NTASWFTAL interacted with most human leukocyte antigen (HLA) that are encoded by MHC class I molecules. Further, molecular docking analysis unveiled that NTASWFTAL possessed a greater affinity towards HLA and also available in a greater range of the population. Our study provides a consolidated base for vaccine design and we hope that this computational analysis will pave the way for designing novel vaccine candidates.


title: EFL Classes Must Go Online! Teaching Activities and Challenges during COVID-19 Pandemic in Indonesia

text: In view of the COVID-19 pandemic and government policy to carry out online learning, the present research is aimed at investigating how EFL teachers carry out online EFL learning and its challenges 16 EFL teachers volunteered to participate in this research through invitation The EFL teachers were requested to make written reflections regarding their practices in carrying out online EFL learning and the challenges they encounter Five of them were involved in a follow-up interview individually Semi-structured interview was administered Data coding was done and appropriate extracts were informed in results section To validate the data, data coding was done independently by both researchers, continued by several cycles of discussion As results, the EFL teachers have carried out online learning through a series of activities ranging from checking the students' attendance to giving score on the students' works synchronously or asynchronously depending on each school policy Various applications and platforms ranging from learning management system to additional resource are employed However, many problems emerge from the students, the teachers, and the students' parents along with the valid reasons Therefore, the online learning does not run well since it lacks of preparation and planning Implications for better online learning are discussed Future prospective researches are directed and encouraged


title: Public perceptions of COVID-19 in Australia: perceived risk, knowledge, health-protective behaviours, and vaccine intentions

text: Widespread and sustained engagement with health-protective behaviours (i.e., hygiene and distancing) is critical to successfully managing the COVID-19 pandemic. Evidence from previous emerging infectious disease outbreaks points to the role of perceived risk, worry, media coverage, and knowledge in shaping engagement with health-protective behaviours as well as vaccination intentions. The current study examined these factors in 2,174 Australian residents. An online survey was completed between 2-9 March 2020, at an early stage of the COVID-19 outbreak in Australia. Results revealed that two thirds of respondents were at least moderately worried about a widespread COVID-19 outbreak in Australia (which subsequently occurred). Worry about the outbreak and closely following media coverage were consistent predictors of health-protective behaviours (both over the previous month, and intended behaviours in the case of a widespread outbreak) as well as vaccination intentions. Health-behaviour engagement over the previous month was lower in some demographic groups, including males and younger individuals (18-29 age group). These was a substantial mismatch between respondents' expected symptoms of infection and emerging evidence that a meaningful proportion of people who contract the novel coronavirus will experience asymptomatic infection (i.e., they will not experience symptoms associated with COVID-19). Only 0.3% of those in the current study believed that they personally would not experience any symptoms if they were infected. Uncertainty and misconceptions about COVID-19 were common, including one third of respondents who reported being unsure whether people are likely have natural or existing immunity. There was also uncertainty around whether specific home remedies (e.g., vitamins, saline rinses) would offer protection, whether the virus could spread via the airborne route, and whether the virus was human made and deliberately released. Such misconceptions are likely to cause concern for members of the public. These results point to areas of uncertainty that could be usefully targeted by public education campaigns, as well as psychological and demographic factors associated with engagement with health-protective behaviours. These findings offer potential pathways for interventions to encourage health-protective behaviours to reduce the spread of COVID-19.


title: COVID-19, smoking, and inequalities: a cross-sectional survey of adults in the UK

text: Objectives: To examine associations between smoking and COVID-19 relevant outcomes, taking into account the influence of inequalities and adjusting for potential confounding variables. Design: Online cross-sectional survey. Setting: UK. Participants: 53,002 men and women aged [≥]18y. Main outcome measures: Confirmed and suspected COVID-19, worry about catching and becoming seriously ill from COVID-19, and adherence to protective behaviours. Socioeconomic position was defined according to highest level of education (post-16 qualifications: yes/no). Results: Compared with never smokers (0.3% [95%CI 0.2-0.3%]), prevalence of confirmed COVID-19 was higher among current (0.6% [0.4-0.8%]) but not ex-smokers (0.2% [0.2-0.3%]). The associations were similar before (current: OR 2.14 [1.49-3.08]; ex-smokers: OR 0.73 [0.47-1.14]) and after (current: OR 1.79 [1.22-2.62]; ex-smokers: OR 0.85 [0.54-1.33]) adjustment for potential confounders. For current smokers, this was moderated by socioeconomic position, with higher rates relative to never smokers only seen in those without post-16 qualifications (OR 3.53 [2.04-6.10]). After including suspected cases, prevalence was higher among current smokers (11.2% [10.6-11.9%], OR 1.11 [1.03-1.20]) and ex-smokers (10.9% [10.4-11.5%], OR 1.07 [1.01-1.15]) than never smokers (10.2% [9.9-10.6%]), but remained higher only among ex-smokers after adjustment (OR 1.21 [1.13-1.29]). Current and ex-smokers had higher odds than never smokers of reporting significant stress about catching (current: OR 1.43 [1.35-1.52]; ex-smokers: OR 1.15 [1.09-1.22]) or becoming seriously ill from COVID-19 (current: OR 1.34 [1.27-1.43]; ex-smokers: OR 1.22 [1.16-1.28]). Adherence to recommendations to prevent the spread of COVID-19 was generally high (96.3% [96.1-96.4%]), but lower among current than never smokers (OR 0.70 [0.62-0.78]). Conclusions: When assessed by self-report in a population sample, current smoking was independently associated with confirmed COVID-19 infection. There were socioeconomic disparities, with the association only apparent among those without post-16 qualifications. Smokers reported lower adherence to guidelines despite being more worried than non-smokers about catching or becoming seriously ill from COVID-19.


title: Epidemiology of seasonal coronaviruses: Establishing the context for COVID-19 emergence

text: Public health preparedness for coronavirus disease 2019 (COVID-19) is challenging in the absence of setting-specific epidemiological data. Here we describe the epidemiology of seasonal human coronaviruses (sCoVs) and other cocirculating viruses in the West of Scotland, UK. We analyzed routine diagnostic data for >70,000 episodes of respiratory illness tested molecularly for multiple respiratory viruses between 2005 and 2017. Statistical associations with patient age and sex differed between CoV-229E, CoV-OC43 and CoV-NL63. Furthermore, the timing and magnitude of sCoV outbreaks did not occur concurrently and coinfections were not reported. With respect to other cocirculating respiratory viruses, we found evidence of positive, rather than negative, interactions with sCoVs. These findings highlight the importance of considering cocirculating viruses in the differential diagnosis of COVID-19. Further work is needed to establish the occurrence/degree of cross-protective immunity conferred across sCoVs and with COVID-19, as well as the role of viral coinfection in COVID-19 disease severity.