title: Emerging phylogenetic structure of the SARS-CoV-2 pandemic

text: Since spilling over into humans, SARS-CoV-2 has rapidly spread across the globe, accumulating significant genetic diversity. The structure of this genetic diversity, and whether it reveals epidemiological insights, are fundamental questions for understanding the evolutionary trajectory of this virus. Here we use a recently developed phylodynamic approach to uncover phylogenetic structures underlying the SARS-CoV-2 pandemic. We find support for three SARS-CoV-2 lineages co-circulating, each with significantly different demographic dynamics concordant with known epidemiological factors. For example, Lineage C emerged in Europe with a high growth rate in late February, just prior to the exponential increase in cases in several European countries. Mutations that characterize Lineage C in particular are non-synonymous and occur in functionally important gene regions responsible for viral replication and cell entry. Even though Lineages A and B had distinct demographic patterns, they were much more difficult to distinguish. Continuous application of phylogenetic approaches to track the evolutionary epidemiology of SARS-CoV-2 lineages will be increasingly important to validate the efficacy of control efforts and monitor significant evolutionary events in the future.


title: Detection and Isolation of SARS-CoV-2 in Serum, Urine, and Stool Specimens of COVID-19 Patients from the Republic of Korea

text: OBJECTIVES: Coronavirus Disease-19 (COVID-19) is a respiratory infection characterized by the main symptoms of pneumonia and fever. It is caused by the novel coronavirus severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), which is known to spread via respiratory droplets. We aimed to determine the rate and likelihood of SARS-CoV-2 transmission from COVID-19 patients through non-respiratory routes. METHODS: Serum, urine, and stool samples were collected from 74 hospitalized patients diagnosed with COVID-19 based on the detection of SARS-CoV-2 in respiratory samples. The SARS-CoV-2 RNA genome was extracted from each specimen and real-time reverse transcription polymerase chain reaction performed. CaCo-2 cells were inoculated with the specimens containing the SARS-COV-2 genome, and subcultured for virus isolation. After culturing, viral replication in the cell supernatant was assessed. RESULTS: Of the samples collected from 74 COVID-19 patients, SARS-CoV-2 was detected in 15 serum, urine, or stool samples. The virus detection rate in the serum, urine, and stool samples were 2.8% (9/323), 0.8% (2/247), and 10.1% (13/129), and the mean viral load was 1,210 ± 1,861, 79 ± 30, and 3,176 ± 7,208 copy/μL, respectively. However, the SARS-CoV-2 was not isolated by the culture method from the samples that tested positive for the SARS-CoV-2 gene. CONCLUSION: While the virus remained detectable in the respiratory samples of COVID-19 patients for several days after hospitalization, its detection in the serum, urine, and stool samples was intermittent. Since the virus could not be isolated from the SARS-COV-2-positive samples, the risk of viral transmission via stool and urine is expected to be low.


title: No Evidence for Temperature-Dependence of the COVID-19 Epidemic

text: The pandemic of the COVID-19 disease extended from China across the north-temperate zone, and more recently to the tropics and southern hemisphere. We find no evidence that spread rates decline with temperatures above 20 oC, suggesting that the COVID-19 disease is unlikely to behave as a seasonal respiratory virus.


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ACE2 expression and sex disparity in COVID-19


docid: wbyqmvhs

title: Multiple approaches for massively parallel sequencing of HCoV-19 (SARS-CoV-2) genomes directly from clinical samples

text: COVID-19 has caused a major epidemic worldwide, however, much is yet to be known about the epidemiology and evolution of the virus. One reason is that the challenges underneath sequencing HCoV-19 directly from clinical samples have not been completely tackled. Here we illustrate the application of amplicon and hybrid capture (capture)-based sequencing, as well as ultra-high-throughput metatranscriptomic (meta) sequencing in retrieving complete genomes, inter-individual and intra-individual variations of HCoV-19 from clinical samples covering a range of sample types and viral load. We also examine and compare the bias, sensitivity, accuracy, and other characteristics of these approaches in a comprehensive manner. This is, to date, the first work systematically implements amplicon and capture approaches in sequencing HCoV-19, as well as the first comparative study across methods. Our work offers practical solutions for genome sequencing and analyses of HCoV-19 and other emerging viruses.


title: Simulating a community mental health service during the COVID-19 pandemic: effects of clinician-clinician encounters, clinician-patient-family encounters, symptom-triggered protective behaviour, and household clustering

text: Background. Face-to-face healthcare, including psychiatric provision, must continue despite reduced interpersonal contact during the COVID-19 (SARS-CoV-2 coronavirus) pandemic. Community-based services might use domiciliary visits, consultations in healthcare settings, or remote consultations. Services might also alter direct contact between clinicians. Aims. We examined the effects of appointment types and clinician-clinician encounters upon infection rates. Methods. We modelled a COVID-19-like disease in a hypothetical community healthcare team, their patients, and patients' household contacts (family). In one condition, clinicians met patients and briefly met family (e.g. home visit or collateral history). In another, patients attended alone (e.g. clinic visit), segregated from each other. In another, face-to-face contact was eliminated (e.g. videoconferencing). We also varied clinician-clinician contact; baseline and ongoing "external" infection rates; whether overt symptoms reduced transmission risk behaviourally (e.g. via personal protective equipment, PPE); and household clustering. Results. Service organization had minimal effects on whole-population infection under our assumptions but materially affected clinician infection. Appointment type and inter-clinician contact had greater effects at low external infection rates and without a behavioural symptom response. Clustering magnified the effect of appointment type. We discuss infection control and other factors affecting appointment choice and team organization. Conclusions. Distancing between clinicians can have significant effects on team infection. Loss of clinicians to infection likely has an adverse impact on care, not modelled here. Appointments must account for clinical necessity as well as infection control. Interventions to reduce transmission risk can synergize, arguing for maximal distancing and behavioural measures (e.g. PPE) consistent with safe care.


title: Bioenergy Crisis in Coronavirus Diseases?

text: Coronavirus disease (COVID-19) has been declared as a pandemic by the World Health Organization (WHO).[...].


title: Extended use or re-use of single-use surgical masks and filtering facepiece respirators: A rapid evidence review

text: Background The COVID-19 pandemic has led to unprecedented demand for personal protective equipment. Shortages of surgical masks and filtering facepiece respirators has led to the extended use or re-use of single-use respirators and surgical masks by frontline healthcare workers. The evidence base underpinning such practices has been questioned. Objectives To summarise guidance and synthesise systematic review evidence on extended use, re-use or reprocessing of single-use surgical masks or filtering facepiece respirators. Methods A targeted search of the World Health Organization, European Centre for Disease Prevention and Control, the US Centers for Disease Control and Prevention, and Public Health England websites was conducted to identify guidance. Four databases (Medline, Pubmed, Epistemonikos, Cochrane Database of Systematic Reviews) and three preprint repositories (Litcovid, MedRxiv and Open Science Framework) were searched for relevant systematic reviews. Record screening and data extraction was conducted by two reviewers. Quality of included systematic reviews was appraised using the AMSTAR-2 checklist. Findings were integrated and narratively synthesised to highlight the extent to which key claims in guidance documents were supported by research evidence. Results Six guidance documents were identified. All note that extended use or re-use of single-use surgical masks and respirators (with or without reprocessing) should be considered only in situations of critical shortage. Extended use was generally favoured over re-use because of reduced risk of contact transmission. Four high-quality systematic reviews were included: three focused on reprocessing (decontamination) of N95 respirators and one focused on reprocessing of surgical masks. There was limited evidence on the impact of extended use on masks and respirators. Vaporised hydrogen peroxide and ultraviolet germicidal irradiation were highlighted as the most promising reprocessing methods, but evidence on the relative efficacy and safety of different methods was limited. We found no well-established methods for reprocessing respirators at scale. Conclusions: There is limited evidence on the impact of extended use and re-use of surgical masks and respirators. Where extended use or re-use is being practiced, healthcare organisations should ensure that policies and systems are in place to ensure these practices are carried out safely and in line with available guidance.


title: COVID-19-related Fake News in Social Media

text: This study analyzes N=125 prominent fake news related to the COVID-19 pandemic spread in social media from 29 January to 11 April 2020. The five parameters of the analysis are themes, content types, sources, coverage, and intentions. First, the six major themes of fake news are health, religiopolitical, political, crime, entertainment, religious, and miscellaneous. Health-related fake news (67.2%) dominates the others. Second, the seven types of fake news contents have four main types: text, photo, audio and video, and three combined types: text & photo; text & video; and text & photo & video. More fake news takes the forms of text & video (47.2%), while the main types of content are less popular. Third, the two main sources of fake news are online media and mainstream media, where online-produced fake news (94.4%) prevails. Fourth, the main two types of coverages are international and national, and more fake news has an international connection (54.4%). Fifth, the intention of fake news has three types: positive, negative, and unknown. Most of the COVID-19-related fake news is negative (63.2%). Although fake news cases are unevenly distributed and repeatedly fluctuates during the period, a slow decrease of daily cases is noticed toward the end.


title: Contributions of Latin American researchers in the understanding the novel coronavirus outbreak: A literature review

text: This paper aimed to give the visibility of Latin American researchers' contributions to the comprehension of COVID-19; our method was a literature review. Currently, the world is facing a health and socioeconomic crisis caused by the novel coronavirus, SARS-CoV-2, and its disease COVID-19. Therefore, in less than four months, researchers have published a significant number of articles related to this novel virus. For instance, a search focused on the Scopus database on April 10, 2020, showed 1224 documents published by authors with 1797 affiliations from 80 countries. 25.4%, 24.0%, and 12.6% of these national affiliations were from China, Europe, and the USA, respectively, making these regions leaders in COVID-19 research. In the case of Latin America, on April 10, 2020, we searched different databases, such as Scopus, PubMed, and Web of Science, finding that the contribution of this region was 2.7% of the total publications found. In other words, we found 153 publications related to COVID-19 with at least one Latin American researcher. We summarized and processed the information from these 153 publications, finding active participation in topics like medical, social, and environmental considerations, bioinformatics, and epidemiology.


title: Deducing the Dose-response Relation for Coronaviruses from COVID-19, SARS and MERS Meta-analysis Results

text: The fundamental dose-response relation is still missing for better evaluating and controlling the transmission risk of COVID-19. A recent study by Chu et al. has indicated that the anticipated probability of viral infection is about 12.8% within 1 m and about 2.6% at further distance through a systematic review and meta-analysis. This important information provides us a unique opportunity to assess the dose-response relation of the viruses, if reasonable exposure dose could be estimated. Here we developed a simple framework to integrate the a priori dose-response relation for SARS-CoV based on mice experiments, and the recent data on infection risk and viral shedding, to shed light on the dose-response relation for human. The developed dose-response relation is an exponential function with a constant k in the range of 6.19E4 to 7.28E5 virus copies. The result mean that the infection risk caused by one virus copy in viral shedding is about 1.5E-6 to 1.6E-5. The developed dose-response relation provides a tool to quantify the magnitude of the infection risk.


We're calling for changes to the contact tracing programme for veterinary practices


title: Consensus Statement On Immune Modulation in Multiple Sclerosis and Related Disorders During the COVID-19 Pandemic: Expert Group on Behalf of the Indian Academy of Neurology

text: Knowledge related to SARS-CoV-2 or 2019 novel coronavirus (2019-nCoV) is still emerging and rapidly evolving. We know little about the effects of this novel coronavirus on various body systems and its behaviour among patients with underlying neurological conditions, especially those on immunomodulatory medications. The aim of the present consensus expert opinion document is to appraise the potential concerns when managing our patients with underlying CNS autoimmune demyelinating disorders during the current COVID-19 pandemic.


title: One score to rule them all: severity assessment in laboratory mice

text: Animal welfare and the refinement of experimental procedures are fundamental aspects of biomedical research. They provide the basis for robust experimental designs and reproducibility of results. In many countries, the determination of welfare is a mandatory legal requirement and implies the assessment of the degree of the severity that an animal experiences during an experiment. However, for an effective severity assessment, an objective and exact approach/system/strategy is needed. In light of these demands, we have developed the Relative Severity Assessment (RELSA) score. This comprehensive composite score was established on the basis of physiological and behavioral data from a surgical mouse study. Body weight, the Mouse Grimace Scale score, burrowing behavior, and the telemetry-derived parameters heart rate, heart rate variability, temperature, and general activity were used to investigate the quality of indicating severity during postoperative recovery. The RELSA scores not only revealed individual severity levels but also allowed a comparison of severity in distinct mouse models addressing colitis, sepsis, and restraint stress using a k-means clustering approach with the maximum achieved RELSA scores. We discriminated and classified data from sepsis nonsurvivors into the highest relative severity level. Data from mice after intraperitoneal transmitter implantation and sepsis survivor al were located in the next lower cluster, while data from mice subjected to colitis and restraint stress were placed in the lowest severity cluster. Analysis of individual variables and their combinations revealed model- and time-dependent contributions to severity levels. In conclusion, we propose the RELSA score as a validated tool for objective real-time applicability in severity assessment and as a first step towards a unified and accessible risk assessment tool in biomedical research. As an effective severity assessment system, it will fundamentally improve animal welfare, as well as data quality and reproducibility.


title: Negative nasopharyngeal SARS-CoV-2 PCR conversion in Response to different therapeutic interventions

text: BACKGROUND: Despite lack of convincing evidence of the efficacy of hydroxychloroquine, it has been suggested to be used for the treatment of SARS CoV 2 to accelerate the negative virus conversion. We aimed to explore the association between negative nasopharyngeal SARS CoV 2 PCR clearance and different therapeutic interventions. METHODOLOGY: This was a retrospective cohort study of 93 patients who were admitted to medical ward with a PCR confirmed diagnosis of COVID 19 and met the inclusion criteria in a tertiary hospital in Mecca, Saudi Arabia. There were three interventional subgroups (group A (n=45): who received antimalarial drug only classified as (A1), combined with azithromycin (A2) or combined with antiviral drugs (A3)), and one supportive care group (group B) (n=48). The primary and secondary endpoints of the study were achieving negative SARS_CoV_2 nasopharyngeal PCR sample within five days or less from the start of the intervention and 12 days or less from the diagnose, respectively. RESULTS: The mean age of the patients was 43.9 years (SD:15.9). A median time of 3.00 days (IQR:2.00 to 6.50) needed from the time of starting the intervention/supportive care to the first negative PCR sample. There was no statistically significant difference neither between the percentage of patients in the interventional group and the supportive care group who achieved the primary or the secondary endpoint, nor in the median time needed to achieve the first negative PCR sample (p>0.05). CONCLUSION: Prescribing antimalarial medications was not shown to shorten the disease course nor to accelerate the negative PCR conversion rate.


title: ASGN: An Active Semi-supervised Graph Neural Network for Molecular Property Prediction

text: Molecular property prediction (e.g., energy) is an essential problem in chemistry and biology. Unfortunately, many supervised learning methods usually suffer from the problem of scarce labeled molecules in the chemical space, where such property labels are generally obtained by Density Functional Theory (DFT) calculation which is extremely computational costly. An effective solution is to incorporate the unlabeled molecules in a semi-supervised fashion. However, learning semi-supervised representation for large amounts of molecules is challenging, including the joint representation issue of both molecular essence and structure, the conflict between representation and property leaning. Here we propose a novel framework called Active Semi-supervised Graph Neural Network (ASGN) by incorporating both labeled and unlabeled molecules. Specifically, ASGN adopts a teacher-student framework. In the teacher model, we propose a novel semi-supervised learning method to learn general representation that jointly exploits information from molecular structure and molecular distribution. Then in the student model, we target at property prediction task to deal with the learning loss conflict. At last, we proposed a novel active learning strategy in terms of molecular diversities to select informative data during the whole framework learning. We conduct extensive experiments on several public datasets. Experimental results show the remarkable performance of our ASGN framework.


title: Comparison of epidemiological characteristics of COVID-19 patients in Vietnam

text: Background. There are limited data on COVID-19 patients in Vietnam. The paper examined and compared epidemiological characteristics of COVID-19 patients in Vietnam. Methods. The data was obtained using publicly available information from the official website of Vietnam Ministry of Health covering a period of 01/23/2020 to 05/27/2020. T-test, Chi-square test and Fishers Exact test were utilized to compare characteristics of COVID-19 patients between under-treatment and discharge groups and between overseas and non-overseas travel groups. Results. Vietnam had a total of 327 cases of COVID-19 as of May 27, 2020. The median age of patients was 30 years (ranging from 3 months to 88 years). About 68% of patients (n=223) had acquired the disease outside the country while 32% were infected within the country. Among those infected inside the country, 66% were women. Men were more likely than women to be infected from overseas (p<0.001). Younger patients were significantly associated with international travel (p=.001). While patients in the South reported highest levels of overseas travel history (77.9%), those (100%) in the Central reporting the highest level of being discharged (p<0.001). Women (54.7%) had a higher rate of discharge compared to men (45.3%) [p<0.001]. Nearly 86% have recovered and discharged from hospitals. There has been no reported fatality. Conclusion. A majority of COVID-19 cases in Vietnam were acquired from abroad. A significantly higher number of women than men were infected inside the country calling for further research about gender disparities in the fight against COVID-19 in Vietnam.


title: On the impact of early non-pharmaceutical interventions as containment strategies against the COVID-19 pandemic

text: Background The novel coronavirus SARS-CoV-2 (COVID-19) emerged in December 2019 in Wuhan, China and has spread since then to around 210 countries and territories by April 2020. Consequently, countries have adopted physical distance measures in an attempt to mitigate the uncontrolled spread of the virus. A critical question for policymakers to inform evidence-based practice is if and how physical distance measures slowed the propagation of COVID-19 in the early phase of the pandemic. Methods This study aims to quantify the effects of physical distance mitigation measures on the propagation of the COVID-19 pandemic. Data from John Hopkins University on confirmed cases and testing data from the Our World in Data were used in an interrupted time series analysis to estimate the effects of physical distance measures on the growth rates of the pandemic in 12 countries of Asia, Africa, and Europe. Findings We found that physical distance measures produced a significant decrease in the growth rates of the COVID-19 pandemic in five countries (Austria, Belgium, Italy, Malaysia, and South Korea). The test-positivity rate was significant in understanding the slowing growth rate of COVID-19 cases caused by the mitigation measures, as it provides important context that is missing from analysis based only on confirmed case data. Interpretation Physical distance interventions effectively slowed the progression of the COVID-19 pandemic. The results of this study could inform infectious disease mitigation policies based on physical distance measures by quantifying the differential health outcomes of a pandemic with and without physical distance interventions.


title: COVID-19 Epidemic Outside China: 34 Founders and Exponential Growth

text: Background: In December 2019, pneumonia infected with a novel coronavirus burst in Wuhan, China. Now the situation is almost controlled in China but is worse outside China. We aimed to build a mathematical model to capture the global trend of epidemics outside China. Methods: In this retrospective, outside-China diagnosis number reported from Jan 21 to Feb 28, 2020 was downloaded from WHO website. We develop a simple regression model on these numbers: log10 (Nt+34)=0.0515*t+2.075 where Nt is the total diagnosed patient till the ith day, t=1 at Feb 1. Findings: Based on this model, we estimate that there have been about 34 unobserved founder patients at the beginning of spread outside China. The global trend is approximately exponential, with the rate of 10 folds every 19 days.


title: Validation of a commercially available SARS-CoV-2 serological Immunoassay

text: Aims: To validate the diagnostic accuracy of a Euroimmun SARS-CoV-2 IgG and IgA immunoassay for COVID-19 disease. Methods: In this unmatched (1:1) case-control validation study, we used sera of 181 laboratory-confirmed SARS-CoV-2 cases and 176 negative controls collected before the emergence of SARS-CoV-2. Diagnostic accuracy of the immunoassay was assessed against a whole spike protein-based recombinant immunofluorescence assay (rIFA) by receiver operating characteristic (ROC) analyses. Discrepant cases between ELISA and rIFA were further tested by pseudo-neutralization assay. Results: COVID-19 patients were more likely to be male and older than controls, and 50.3% of them were hospitalized. ROC curve analyses indicated that IgG and IgA had a high diagnostic accuracy with AUCs of 0.992 (95% Confidence Interval [95%CI]: 0.986-0.996) and 0.977 (95%CI: 0.963-0.990), respectively. IgG assays outperformed IgA assays (p=0.008). Considering optimized cut-offs taking the 15% inter-assay imprecision assessed into account, an IgG ratio cut-off > 1.5 displayed a 100% specificity (95%CI: 98-100) and a 100% positive predictive value (95%CI: 97-100). A 0.5 cut-off displayed a 97% sensitivity (95%CI: 93-99) and a 97% negative predictive value (95%CI: 93-99). Adopting these thresholds, rather than those of the manufacturer, improved assay performance, leaving 12% of IgG ratios ranging between 0.5-1.5 as indeterminate. Conclusions: The Euroimmun assay displays a nearly optimal diagnostic accuracy using IgG against SARS-CoV-2 in a samples of patients, without any obvious gains from considering IgA serology. The optimized cut-offs are fit for rule-in and rule-out purposes, allowing determination of whether individuals have been exposed to SARS-CoV-2 or not in our study population. They should however not be considered as a surrogate of protection at this stage.


title: Mechanical ventilation utilization in COVID-19: A systematic review and meta-analysis

text: Background: In December 2019, SARS-CoV-2 caused a global pandemic with a viral infection called COVID19. The disease usually causes respiratory symptoms but in a small proportion of patients can lead to pneumonitis, Adult Respiratory Distress Syndrome and death. Invasive Mechanical Ventilation (IMV) is considered a life-saving treatment for COVID19 patients and a huge demand for IMV devices was reported globally. This review aims to provide insight into the initial IMV practices for COVID19 patients in the initial phase of the pandemic. Methods: Electronic databases (Embase and MEDLINE) were searched for applicable articles using relevant keywords. The references of included articles were hand searched. Articles that reported the use of IMV in adult COVID19 patients were included in the review. The NIH quality assessment tool for cohort and cross-sectional studies was used to appraise studies. Results: 106 abstracts were identified from the databases search, of which 16 were included. 5 studies were included in the meta-analysis. In total, 9988 patients were included across all studies. The overall cases of COVID-19 requiring IMV ranged from 2-77%. Increased age and pre-existing comorbidities increased the likelihood of IMV requirement. The reported mortality rate in patients receiving IMV ranged between 50-100%. On average, IMV was required and initiated between 10-17 days from symptoms onset. When ventilated, COVID19 patients required IMV for a median of 10-17 days across studies. Little information was provided on ventilatory protocols or management strategies. Conclusion: In these initial reporting studies for the first month of the pandemic, patients receiving IMV were older and had more pre-existing co-morbidities than those who did not require IMV. The mortality rate was high in COVID19 patients who received IMV. Studies are needed to evaluate protocols and modalities of IMV to improve outcomes and identify the populations most likely to benefit from IMV.


docid: ommypdxh

title: Predicting Disease Progression in COVID19: A Score Based On Lab Tests At Time Of Diagnosis

text: Background COVID19 is worldwide pandemic that is mild in the majority of patients but can result in a pneumonia like illness with progression to acute respiratory distress syndrome and death. Predicting the disease severity at time of diagnosis can be helpful in prioritizing hospital admission and resources. Methods We prospectively recruited 1096 consecutive patients with COVID19 from the Jaber Hospital, a COVID19 facility in Kuwait, between 24 February and 20 April 2020. The primary endpoint of interest was disease severity defined algorithmically. Predefined risk variables were collected at the time of PCR based diagnosis of the infection. Prognostic model development used 5-fold cross-validated regularized logit regression. The cohort was divided into a training and validation cohort and all model development proceeded on the training cohort. Results There were 643 patients with clinical course data of whom 94 developed severe COVID19. In the final model, age, CRP, procalcitonin, lymphocyte and monocyte percentages and serum albumin were independent predictors of a more severe illness course. The final prognostic model demonstrated good discrimination, calibration and internal validity. Conclusion We developed and validated a simple score calculated at time of diagnosis that can predict patients with severe COVID19 disease. Keywords COVID-19, Adverse Outcome, mortality, Procalcitonin, health policy


Offline: COVID-19—what countries must do now


title: Structural Basis for the Inhibition of the RNA-Dependent RNA Polymerase from SARS-CoV-2 by Remdesivir

text: The pandemic of Corona Virus Disease 2019 (COVID-19) caused by SARS-CoV-2 has become a global crisis. The replication of SARS-CoV-2 requires the viral RNA-dependent RNA polymerase (RdRp), a direct target of the antiviral drug, Remdesivir. Here we report the structure of the SARS-CoV-2 RdRp either in the apo form or in complex with a 50-base template-primer RNA and Remdesivir at a resolution range of 2.5-2.8 Å. The complex structure reveals that the partial double-stranded RNA template is inserted into the central channel of the RdRp where Remdesivir is incorporated into the first replicated base pair and terminates the chain elongation. Our structures provide critical insights into the working mechanism of viral RNA replication and a rational template for drug design to combat the viral infection.


title: The Effects of "Fangcang, Huoshenshan, and Leishenshan" Makeshift Hospitals and Temperature on the Mortality of COVID-19

text: Background In December 2019, a novel coronavirus disease (COVID-19) broke out in Wuhan, China, however, the factors affecting the mortality remain unclear. Methods Thirty-two days of data that were shared by China National Health Commission and China Weather Net were collected using standard forms. The difference in the mortality of confirmed and severe cases before and after the use of Fangcang, Huoshenshan, and Leishenshan makeshift hospitals (MSHs) was tested using Mann-Whitney U test. We also studied whether air temperature (AT) could affect the above outcomes of COVID-19 cases by performing Spearman analysis. Results The mortality of confirmed cases was significantly decreased both in Wuhan (U = 1, P < 0.001) and Hubei (U = 0, P < 0.001), while in non-Hubei regions, as a contrast, the mortality of confirmed cases remained unchanged (U = 40, P = 0.139). However, another eight days later, changes in the mortality in non-Hubei regions also became significant (U = 73, P = 0.039). Mortality of confirmed cases was found to be significantly correlated with temperature both in Wuhan (r = -0.441, P = 0.012) and Hubei (r = -0.440, P = 0.012). Conclusions Our findings indicated that both the use of MSHs and the rise of AT were beneficial to the survival of COVID-19 cases.


title: Appendix Case Study: The Spring 2009 Swine Influenza Outbreak

text: Unknown


docid: ossmgzzn

title: COVID-19 knowledge, risk perception and precautionary behaviour among Nigerians: A moderated mediation approach

text: ABSTRACT Introduction: Individuals who have knowledge of an infectious disease and also perceive the risks associated with such infectious disease tend to engage more in precautionary behaviour; however, little is known about this association as it relates to the novel Coronavirus (COVID-19). There is possibility of moderated mediation effect in the association between these variables. Objectives: To examine whether risk perception determines the association between COVID-19 knowledge and precautionary behaviour among Nigerians, taking into consideration the gender differentials that may exist in the process. Design: A web-based cross-sectional study. Setting: Participants were recruited via social media platform, WhatsApp using google form from March 28 to April 4, 2020. Participants: 1500-Nigerian (mean age =27.43, SD=9.75 with 42.7% females and 57.3% males) were recruited from 180 cities in Nigeria using snowball sampling technique. They responded to an online survey form comprising demographic questions and adapted versions of the Ebola knowledge scale, SARS risk perception scale and a precautionary behavior scale. Result: Moderated mediation analysis showed that risk perception mediated the association between COVID-19 knowledge and precautionary behavior and this indirect effect was moderated by gender. Having correct knowledge of COVID-19 was linked to higher involvement in precautionary behavior through risk perception for females but not for males. COVID-19 awareness campaigns may target raising more awareness of the risks associated with the infection in order to make individuals engage more in precautionary behaviors. Conclusion: Awareness campaigns and psychological intervention strategies may be particularly important at the moment, for males more than females.


title: KCDC Risk Assessments on the Initial Phase of the COVID-19 Outbreak in Korea

text: OBJECTIVES: This study aims to evaluate the risk assessments of coronavirus 2019 (COVID-19) in the Korea Centers for Disease Control and Prevention (KCDC), from the point of detection to the provision of basic information to the relevant public health authorities. METHODS: To estimate the overall risk of specific public health events, probability, and impact at the country-level were evaluated using available information. To determine the probability of particular public health events, the risk of importation and risk of transmission were taken into consideration. KCDC used 5 levels (“very low,” “low,” “moderate,” “high,” and “very high”) for each category and overall risk was eventually decided. RESULTS: A total of 8 risk assessments were performed on 8 separate occasions between January 8(th) to February 28(th), 2020, depending on the detection and report of COVID-19 cases in other countries. The overall risk of the situation in each assessment increased in severity over this period: “low” (first), “moderate” (second), “high” (third), “high” (fourth), “high” (fifth), “high” (sixth), “high” (seventh), and “very high” (eighth). CONCLUSION: The KCDC’s 8 risk assessments were utilized to activate national emergency response mechanisms and eventually prepare for the pandemic to ensure the containment and mitigation of COVID-19 with non-pharmaceutical public health measures.


title: Analyses of spike protein from first deposited sequences of SARS-CoV2 from West Bengal, India

text: India has recently started sequencing SARS-CoV2 genome from clinical isolates. Currently only few sequences are available from three states in India. Kerala was the first state to deposit complete sequence from two isolates followed by one from Gujarat. On April 27, 2020, the first five sequences from the state of West Bengal (Eastern India) were deposited on ‘a global initiative on sharing avian flu data’ (GISAID) platform. In this paper we have analysed the spike protein sequences from all these five isolates and also compared for their similarities or differences with other sequences reported in India and with isolates of Wuhan origin. We report one unique mutation at position 723 and the other at 1124 in the S2 domain of spike protein of the isolates from West Bengal only and one mutation downstream of the receptor binding domain at position 614 in S1 domain which was common with the sequence from Gujarat (a state of western part of India). Mutation in the S2 domain showed changes in the secondary structure of the spike protein at region of mutation. We also studied molecular dynamics using normal mode analyses and found that this mutation decreases the flexibility of S2 domain. Since both S1 and S2 are important in receptor binding followed by entry in the host cells, such mutations may define the affinity or avidity of receptor binding.


title: Green tea and Spirulina extracts inhibit SARS, MERS, and SARS-2 spike pseudotyped virus entry in vitro

text: Coronaviruses (CoVs) infect a wide range of animals and birds. Their tropism is primarily determined by the ability of the spike (S) protein to bind to a host cell surface receptor. The rapid outbreak of emerging novel coronavirus, SARS-CoV 2 in China inculcates the need for the development of hasty and effective intervention strategies. Medicinal plants and natural compounds have been traditionally used to treat viral infections. Here, we generated VSV based pseudotyped viruses (pvs) of SARS-, MERS-, and SARS-2 CoVs to screen entry inhibitors from natural products. In the first series of experiments, we demonstrated that pseudotyped viruses specifically bind on their receptors and enter into the cells. SARS and MERS polyclonal antibodies neutralize SARSpv and SARS-2pv, and MERSpv respectively. Incubation of soluble ACE2 inhibited entry of SARS and SARS-2 pvs but not MERSpv. In addition, expression of ACE2 and DPP4 in non-permissive BHK21 cells enabled infection by SARSpv, SARS-2pv, and MERSpv respectively. Next, we showed the antiviral properties of known enveloped virus entry inhibitors, Spirulina and Green tea extracts against CoVpvs. SARSpv, MERSpv, and SARS-2pv entry were blocked with higher efficiency when preincubated with either green tea or spirulina extracts. Green tea provided a better inhibitory effect than the spirulina extracts by binding to the S1 domain of spike and blocking the interaction of spike with its receptor. Further studies are required to understand the exact mechanism of viral inhibition. In summary, we demonstrate that pseudotyped virus is an ideal tool for screening viral entry inhibitors. Moreover, spirulina and green tea could be promising antiviral agents against emerging viruses.


title: Efficient high throughput SARS-CoV-2 testing to detect asymptomatic carriers

text: The COVID-19 pandemic is rapidly spreading throughout the world. Recent reports suggest that 10-30% of SARS-CoV-2 infected patients are asymptomatic. Other studies report that some subjects have significant viral shedding prior to symptom onset. Since both asymptomatic and pre-symptomatic subjects can spread the disease, identifying such individuals is critical for effective control of the SARS-CoV-2 pandemic. Therefore, there is an urgent need to increase diagnostic testing capabilities in order to also screen asymptomatic carriers. In fact, such tests will be routinely required until a vaccine is developed. Yet, a major bottleneck of managing the COVID-19 pandemic in many countries is diagnostic testing, due to limited laboratory capabilities as well as limited access to genome-extraction and Polymerase Chain Reaction (PCR) reagents. We developed P-BEST - a method for Pooling-Based Efficient SARS-CoV-2 Testing, using a non-adaptive group-testing approach, which significantly reduces the number of tests required to identify all positive subjects within a large set of samples. Instead of testing each sample separately, samples are pooled into groups and each pool is tested for SARS-CoV-2 using the standard clinically approved PCR-based diagnostic assay. Each sample is part of multiple pools, using a combinatorial pooling strategy based on compressed sensing designed for maximizing the ability to identify all positive individuals. We evaluated P-BEST using leftover samples that were previously clinically tested for COVID-19. In our current proof-of-concept study we pooled 384 patient samples into 48 pools providing an 8-fold increase in testing efficiency. Five sets of 384 samples, containing 1-5 positive carriers were screened and all positive carriers in each set were correctly identified. P-BEST provides an efficient and easy-to-implement solution for increasing testing capacity that will work with any clinically approved genome-extraction and PCR-based diagnostic methodologies.


公共衛生緊急事件與2019新型冠狀病毒（COVID-19）之法政議題


title: Utility and limitations of Google searches on sensory loss as markers for new COVID-19 cases

text: Evidence of smell loss in COVID-19 is growing. Researchers and analysts have suggested to use Google searches on smell loss as indicators of COVID-19 cases. However, such searches may be due to interest elicited by media coverage of the COVID-19-related smell loss, rather than attempts to understand self-symptoms. We analyzed searches related to 4 senses: smell and taste (both recently shown to be impaired in some COVID-19 patients), vision and sight (senses not currently known to be impaired in COVID-19 patients), and an additional general control ("COVID-19 symptoms"). Focusing on two countries with a large number of cases, Italy and the United States, we have compared Google Trends results per region or state to the number of new cases prevalence in that region. The analysis was performed for each of the 8 weeks ranging from March 4th till April 28th. No correlation with vision loss or sight loss searches was identified, while taste and smell loss searches were correlated with new COVID-19 cases during a limited time window, that starts when the number of weekly new cases reached for the first time 21357 cases in Italy (11-17 March) and 47553 in the US (18-24 March). Media effect on the specific symptoms searches was also analyzed, establishing a different impact according to the country. Our results suggest that Google Trends for taste loss and smell loss searches captured a genuine connection between these symptoms and new COVID-19 cases prevalence in the population. However, due to variability in correlation from week to week, and overall decrease in correlation as taste and smell loss are becoming known COVID-19 symptoms, recognized now by CDC and World Health Organization, Google Trends is no longer a reliable marker for monitoring the disease spread. The "surprise rise" followed by decrease, probably attributable to knowledge saturation, should be kept in mind for future digital media analyses of potential new symptoms of COVID-19 or future pandemics.


Implication des services de santé au travail dans la lutte contre l’épidémie de COVID 19: nouvelles possibilités de prescription des arrêts de travail, report de certaines visites, participation active à la lutte


title: Rapid and Inexpensive Whole-Genome Sequencing of SARS-CoV-2 using 1200 bp Tiled Amplicons and Oxford Nanopore Rapid Barcoding

text: Rapid and cost-efficient whole-genome sequencing of SARS-CoV-2, the virus that causes COVID-19, is critical for understanding viral transmission dynamics. Here we show that using a new multiplexed set of primers in conjunction with the Oxford Nanopore Rapid Barcode library kit allows for faster, simpler, and less expensive SARS-CoV-2 genome sequencing. This primer set results in amplicons that exhibit lower levels of variation in coverage compared to other commonly used primer sets. Using five SARS-CoV-2 patient samples with Cq values between 20 and 31, we show that high-quality genomes can be generated with as few as 10,000 reads (approximately 5 Mbp of sequence data). We also show that mis-classification of barcodes, which may be more likely when using the Oxford Nanopore Rapid Barcode library prep, is unlikely to cause problems in variant calling. This method reduces the time from RNA to genome sequence by more than half compared to the more standard ligation-based Oxford Nanopore library preparation method at considerably lower costs.


title: Traditional Chinese medicine herbal extracts of Cibotium barometz, Gentiana scabra, Dioscorea batatas, Cassia tora, and Taxillus chinensis inhibit SARS-CoV replication

text: Abstract Development of anti-severe acute respiratory syndrome associated coronavirus (SARS-CoV) agents is pivotal to prevent the reemergence of the life-threatening disease, SARS. In this study, more than 200 extracts from Chinese medicinal herbs were evaluated for anti-SARS-CoV activities using a cell-based assay that measured SARS-CoV-induced cytopathogenic effect (CPE) in vitro on Vero E6 cells. Six herbal extracts, one each from Gentianae Radix (龍膽 lóng dǎn; the dried rhizome of Gentiana scabra), Dioscoreae Rhizoma (山藥 shān yào; the tuber of Dioscorea batatas), Cassiae Semen (決明子 jué míng zǐ; the dried seed of Cassia tora) and Loranthi Ramus (桑寄生 sāng jì shēng; the dried stem, with leaf of Taxillus chinensis) (designated as GSH, DBM, CTH and TCH, respectively), and two from Rhizoma Cibotii (狗脊 gǒu jǐ; the dried rhizome of Cibotium barometz) (designated as CBE and CBM), were found to be potent inhibitors of SARS-CoV at concentrations between 25 and 200μg/ml. The concentrations of the six extracts needed to inhibit 50% of Vero E6 cell proliferation (CC50) and 50% of viral replication (EC50) were determined. The resulting selective index values (SI=CC50/EC50) of the most effective extracts CBE, GSH, DBM, CTH and TCH were>59.4,> 57.5,> 62.1,> 59.4, and>92.9, respectively. Among these extracts, CBM and DBM also showed significant inhibition of SARS-CoV 3CL protease activity with IC50 values of 39μg/ml and 44μg/ml, respectively. Our findings suggest that these six herbal extracts may have potential as candidates for future development of anti-SARS therapeutics.


title: A Targeted Vaccine against COVID-19: S1-Fc Vaccine Targeting the Antigen-Presenting Cell Compartment Elicits Protection against SARS-CoV-2 Infection

text: Vaccination efficacy is enhanced by targeting the antigen-presenting cell compartment. Here, we show that S1-Fc antigen delivery targeting the FcγR+ antigen-presenting cell compartment elicits anti-SARS-CoV-2 S1-antigen specific IgG production in vivo exerting biologically functional and protective activity against live virus infection, assessed in a stringent experimental virus challenge assay in vitro. The S1-domain of the SARS-CoV-2 spike protein was genetically fused to a human immunoglobulin Fc moiety, which contributes to mediate S1-Fc cellular internalization by FcγR+ antigen-presenting cells. Immediately upon administration intramuscularly, our novel vaccine candidate recombinant rS1-Fc homes to lymph nodes in vivo where FcγR+ antigen-presenting cells reside. Seroconversion is achieved as early as day 7, mounting considerably increased levels of anti-S1 IgGs in vivo. Interestingly, immunization at elevated doses with non-expiring S1-Fc encoding dsDNA favors the education of a desired antigen-specific adaptive T cell response. However, low-dose immunization, safeguarding patient safety, using recombinant rS1-Fc, elicits a considerably elevated protection amplitude against live SARS-CoV-2 infection. Our promising findings on rS1-Fc protein immunization prompted us to further develop an affordable and safe product for delivery to our communities in need for COVID-19 vaccinations.


title: Covasim: an agent-based model of COVID-19 dynamics and interventions

text: The COVID-19 pandemic has created an urgent need for models that can project epidemic trends, explore intervention scenarios, and estimate resource needs. Here we describe the methodology of Covasim (COVID-19 Agent-based Simulator), an open-source model developed to help address these questions. Covasim includes demographic information on age structure and population size; realistic transmission networks in different social layers, including households, schools, workplaces, and communities; age-specific disease outcomes; and intrahost viral dynamics, including viral-load-based transmissibility. Covasim also supports an extensive set of interventions, including non-pharmaceutical interventions, such as physical distancing, hygiene measures, and protective equipment; and testing interventions, such as symptomatic and asymptomatic testing, isolation, contact tracing, and quarantine. These interventions can incorporate the effects of delays, loss-to-follow-up, micro-targeting, and other factors. In collaboration with local health agencies and policymakers, Covasim has already been applied to examine disease dynamics and policy options in Africa, Europe, Oceania, and North America.


title: Gaussian Statistics and Data-Assimilated Model of Mortality due to COVID-19: China, USA, Italy, Spain, UK, Iran, and the World Total

text: Covid-19 is characterized by rapid transmission and severe symptoms, leading to deaths in some cases (ranging from 1.5 to 12% of the affected, depending on the country). We identify the Gaussian nature of mortality due to covid-19, as shown in China where it appears to have run its course (during the first sweep of the pandemic at least) and other coutnries, and also in Imperial College modeling. Gaussian distribution involves three parameters, the height, peak location and the width, and the streaming data can be used to infer function value, slope and inflection location as a minimum set of constraints to estimate the subsequent trajectories. Thus, we apply the Gaussian function template as the basis for a data-assimilated model of covid-19 trajectories, first to USA, United Kingdom (UK), Iran and the world total in this study. As more data become available, the Gaussian trajectories are updated, for other nations and also for state-by-state projections in USA.


La comunicación científica y el acceso abierto en la contención de enfermedades: El caso del Coronavirus novel 2019 (2019-nCoV)


docid: csujgaae

title: Stay-at-Home Orders, African American Population, Poverty and State-level Covid-19 Infections: Are there associations?

text: Importance: To cope with the continuing COVID-19 pandemic, state and local health officials need information on the effectiveness of policies aimed at curbing contagion, as well as area-specific socio-demographic characteristics that can portend vulnerability to the disease. Objective: To investigate whether state-imposed stay-at-home orders, African American population in the state, state poverty and other state socio-demographic characteristics, were associated with the state-level incidence of COVID-19 infection. Design, Setting, Participants: State-level, aggregated, publicly available data on positive COVID-19 cases and tests were used. The period considered was March 1st -May 4th. All U.S. states except Washington were included. Outcomes of interest were daily cumulative and daily incremental COVID-19 infection rates. Outcomes were log-transformed. Log-linear regression models with a quadratic time-trend and random intercepts for states were estimated. Covariates included log-transformed test-rates, a binary indicator for stay-at-home, percentage of African American, poverty, percentage elderly, state population and prevalence of selected comorbidities. Binary fixed effects for date each state first started reporting test data were included. Results: Stay-at-home orders were associated with decreases in cumulative ({beta}:-1.23; T-stat: -6.84) and daily ({beta}:-0.46; T-stat: -2.56) infection-rates. Predictive analyses indicated that expected cumulative infection rates would be 3 times higher and expected daily incremental rates about 60% higher in absence of stay-at-home orders. Higher African American population was associated with higher cumulative ({beta}: 0.08; T-stat: 4.01) and daily ({beta}: 0.06; T-stat: 3.50) rates. State poverty rates had mixed results and were not robust to model specifications. There was strong evidence of a quadratic daily trend for cumulative and daily rates. Results were largely robust to alternate specifications. Conclusions: We find evidence that stay-at-home orders, which were widely supported by public-health experts, helped to substantially curb COVID-19 infection-rates. As we move to a phased re-opening, continued precautions advised by public-health experts should be adhered to. Also, a larger African American population is strongly associated with incidence of COVID-19 infection. Policies and resources to help mitigate African American vulnerability to COVID-19 is an urgent public health and social justice issue, especially since the ongoing mass protests against police brutality may further exacerbate COVID-19 contagion in this community.


News: EP Exposed COVID-19 Outbreak at Nursing Home


title: Research on the Influence of Effective Distance Between Cities on the Cross-regional Transmission of COVID-19

text: The COVID-19 epidemic in China has been effectively controlled. It is of great significance to study the law of cross-regional spread of the epidemic, for the prevention and control of the COVID-19 in the future in China and other countries or regions. In this study, the cross-regional connection intensity between cities was characterized based on the probability and the effective distance of the shortest path tree, and the empirical analysis was carried out based on the high-frequency data such as the cases of COVID 19 outbreaks. It is concluded that the higher the intensity of inter-city connection, the larger scale the cross-regional spread of the epidemic.


title: ApoE e4e4 genotype and mortality with COVID-19 in UK Biobank

text: We previously reported that the ApoE e4e4 genotype was associated with COVID-19 test positivity (OR=2.31, 95% CI: 1.65 to 3.24, p=1.19x10-6) in the UK Biobank (UKB) cohort, during the epidemic peak in England, from March 16 to April 26, 2020. With more COVID-19 test results (March 16 to May 31, 2020) and mortality data (to April 26, 2020) linked to UKB, we re-evaluated the ApoE e4 allele association with COVID-19 test positivity, and with all-cause mortality following test-confirmed COVID-19. Logistic regression models compared ApoE e4e4 participants (or e3e4s) to e3e3s with adjustment for sex; age on April 26th or age at death; baseline UKB assessment center in England (accounting for geographical differences in viral exposures); genotyping array type; and the top five genetic principal components (accounting for possible population admixture). ApoE e4e4 genotype was associated with increased risks of test positivity (OR=2.24, 95% CI: 1.72 to 2.93, p=3.24x10-9) and of mortality with test-confirmed COVID-19 (OR=4.29, 95% CI: 2.38 to 7.72, p=1.22x10-6), compared to e3e3s. Independent replications are needed to confirm our findings and mechanistic work is needed to understand how ApoE e4e4 results in the marked increase in vulnerability, especially for COVID-19 mortality. These findings also demonstrate that risks for COVID-19 mortality are not simply related to advanced chronological age or the comorbidities commonly seen in aging.


title: List of acronyms, abbreviations, and definitions

text: Unknown


title: New Epidemiological Model Suggestions Revealing Size of Epidemics Based on the COVID-19 Pandemic Example: Wavelength Models

text: The main purpose of the study is to introduce the wavelength models developed to measure the size of outbreaks based on the COVID-19 example. In this way, the wavelengths of the outbreaks can be calculated, ensuring that the outbreaks are valid, reliable and easy to follow at the national and international level. Wavelength models consist of approved case, death, recovered case and net wavelength models. Thus, the size of the outbreak can be measured both individually and as a whole. COVID-19 cases of 181 countries were used to demonstrate the application of the models. The prominent findings in the applied wavelength models are as follows: the countries with the highest case wavelength are USA, Italy, Spain and Germany, respectively. However, Italy ranks first in the death wavelength, followed by Spain, the USA and France. On the other hand, China has taken the first place in the recovered case wavelength. This country was followed by Spain and Germany and Italy, respectively. Based on all these wavelength models mentioned, net wavelength lengths are calculated. According to the net wavelengths obtained, Canada ranked first, followed by United Kingdom, the USA and the Netherlands, respectively.


title: A Bibliometric Analysis of COVID-19 Research Activity: A Call for Increased Output

text: Background: The novel coronavirus disease 2019 (COVID-19) has impacted many countries across all inhabited continents, and is now considered a global pandemic, due to its high rate of infectivity. Research related to this disease is pivotal for assessing pathogenic characteristics and formulating therapeutic strategies. The aim of this paper is to explore the activity and trends of COVID-19 research since its outbreak in December 2019. Methods: We explored the PubMed database and the World Health Organization (WHO) database for publications pertaining to COVID-19 since December 2019 up until March 18, 2020. Only relevant observational and interventional studies were included in our study. Data on COVID-19 incidence were extracted from the WHO situation reports. Research output was assessed with respect to gross domestic product (GDP) and population of each country. Results: Only 564 publications met our inclusion criteria. These articles came from 39 different countries, constituting 24% of all affected countries. China produced the greatest number of publications with 377 publications (67%). With respect to continental research activity, Asian countries had the highest research activity with 434 original publications (77%). In terms of publications per million persons (PPMPs), Singapore had the highest number of publications with 1.069 PPMPs. In terms of publications per billion-dollar GDP, Mauritius ranked first with 0.075. Conclusion: COVID-19 is a major disease that has impacted international public health on a global level. Observational studies and therapeutic trials pertaining to COVID-19 are essential for assessing pathogenic characteristics and developing novel treatment options.


title: Clinical Considerations in Neurosurgical Radiosurgery in the Time of COVID-19

text: The COVID-19 pandemic is affecting all aspects of the healthcare ecosystem, including administration of stereotactic radiosurgery (SRS). The clinical and logistical challenges created by the COVID-19 public health crisis are clear, but the solutions to these issues are less readily apparent. The goal of this work is to use our experience at a large, academic medical center as a lens for interpreting the many looming issues specific to radiosurgery and its role in the treatment of brain and spine disorders. While the full impact of the pandemic remains to be seen, the aim of this paper is to provide a structural framework to optimize delivery of neurosurgically oriented radiosurgery with proposed clinical workflow strategies. Innovative solutions to the current pandemic crisis affecting the healthcare ecosystem will be driven by increased interdisciplinary and global dialogue.


title: Antimalarials widely used against COVID-19 heighten risk of cardiac arrest. How can doctors minimize the danger?

text: On 19 March, as much of the United States shut down to contain the new coronavirus, genetic cardiologist Michael Ackerman and his wife drove 7 5 hours to retrieve their son from college On the radio, they heard medical experts discussing chloroquine and hydroxychloroquine, two antimalarial drugs that President Donald Trump had just touted at a press briefing, despite no conclusive evidence that they can treat COVID-19 A doctor on the show asserted that the drugs have proved to be completely safe because they’ve been used against malaria for decades and are also used to tame overactive immune cells in lupus and rheumatoid arthritis


title: In silico multi-epitope vaccine against covid19 showing effective interaction with HLA-B*15:03

text: The recent outbreak of severe acute respiratory syndrome (SARS) coronavirus (CoV)-2 (SARS-CoV-2) causing coronavirus disease (covid19) has posed a great threat to human health. Previous outbreaks of SARS-CoV and Middle East respiratory Syndrome CoV (MERS-CoV) from the same CoV family had posed similar threat to human health and economic growth. To date, not even a single drug specific to any of these CoVs has been developed nor any anti-viral vaccine is available for the treatment of diseases caused by CoVs. Subunits present in spike glycoproteins of SARS-CoV and SARS-CoV-2 are involved in binding to human ACE2 Receptor which is the primary method of viral invasion. As it has been observed in the previous studies that there are very minor differences in the spike glycoproteins of SARS-CoV and SARS-CoV-2. SARS-CoV-2 has an additional furin cleavage site that makes it different from SARS-CoV (Walls et al., 2020). In this study, we have analyzed spike glycoproteins of SARS-CoV-2 and SARS-CoV phylogenetically and subjected them to selection pressure analysis. Selection pressure analysis has revealed some important sites in SARS-CoV-2 and SARS-CoV spike glycoproteins that might be involved in their pathogenicity. Further, we have developed a potential multi-epitope vaccine candidate against SARS-CoV-2 by analyzing its interactions with HLA-B*15:03 subtype. This vaccine consists of multiple T-helper (TH) cells, B-cells, and Cytotoxic T-cells (CTL) epitopes joined by linkers and an adjuvant to increase its immunogenicity. Conservation of selected epitopes in SARS, MERS, and human hosts, suggests that the designed vaccine could provide cross-protection. The vaccine is designed in silico by following a reverse vaccinology method acknowledging its antigenicity, immunogenicity, toxicity, and allergenicity. The vaccine candidate that we have designed as a result of this work shows promising result indicating its potential capability of simulating an immune response.


title: Association Between BCG Policy is Significantly Confounded by Age and is Unlikely to Alter Infection or Mortality Rates

text: Recently a number of publications looked at the association between COVID-19 morbidity and mortality on one hand and countries' policies with respect to BCG vaccination on the other. This connection arises from differences in the rates of infection in countries where BCG vaccination is mandatory compared to countries where mandatory vaccination no longer exists or was never implemented in the first place. In at least 2 preprint publications the authors expressed the view that the "known immunological benefits" of BCG vaccination may be behind the biological mechanism of such observation. One study accounted for different income levels in different groups. Another study did not attempted to do so, instead exploring the differences between countries where a booster shot is given vs others where no such practice exists (finding no connection). Both of these studies did not explore other potential confounding factors. Meanwhile the press has focused on these headlines and pushed the narrative that BCG vaccination is causally linked to infection and mortality rates. This poses a serious challenge, demonstrated by the recently initiated clinical trials on BCG vaccination within the COVID19 context. This study shows that population age is a very significant confounding factor that explains the rates of infections much better and has a solid biology mechanism which explains this correlation. It suggests that BCG vaccination may have little or no causal link to infection rates and advises that any follow up studies should control for several confounding factors, such as population age, ethnicity, rates of certain chronic diseases, time from community spread start date, major public policy decisions and income levels.


title: Association Between ACEIs or ARBs Use and Clinical Outcomes in COVID-19 Patients: A Systematic Review and Meta-analysis

text: Importance: There is a controversy regarding whether or not to continue angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with coronavirus disease 2019 (COVID-19). Objective: To evaluate the association between ACEIs or ARBs use and clinical outcomes in COVID-19 patients. Data Sources: Systematic search of the PubMed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials from database inception to May 31, 2020. We also searched the preprint servers medRxiv and SSNR for additional studies. Study Selection: Observational studies and randomized controlled trials reporting the effect of ACEIs or ARBs use on clinical outcomes of adult patients with COVID-19. Data Extraction and Synthesis: Risk of bias of observational studies were evaluated using the Newcastle-Ottawa Scale. Meta-analyses were performed using a random-effects models and effects expressed as Odds ratios (OR) and mean differences with their 95% confidence interval (95%CI). If available, adjusted effects were pooled. Main Outcomes and Measures: The primary outcome was all-cause mortality and secondary outcomes were COVID-19 severity, hospital discharge, hospitalization, intensive care unit admission, mechanical ventilation, length of hospital stay, and troponin, creatinine, procalcitonin, C-reactive protein (CRP), interleukin-6 (IL-6), and D-dimer levels. Results: 40 studies (21 cross-sectional, two case-control, and 17 cohorts) involving 50615 patients were included. ACEIs or ARBs use was not associated with all-cause mortality overall (OR 1.11, 95%CI 0.77-1.60, p=0.56), in subgroups by study design and using adjusted effects. ACEI or ARB use was independently associated with lower COVID-19 severity (aOR 0.56, 95%CI 0.37-0.87, p<0.01). No significant associations were found between ACEIs or ARBs use and hospital discharge, hospitalization, mechanical ventilation, length of hospital stay, and biomarkers. Conclusions and Relevance: ACEIs or ARBs use was not associated with higher all-cause mortality in COVID-19. However, ACEI or ARB use was independently associated with lower COVID-19 severity. Our results support the current international guidelines to continue the use of ACEIs and ARBs in COVID-19 patients with hypertension.


title: Analysing and comparing the COVID-19 data: The closed cases of Hubei and South Korea, the dark March in Europe, the beginning of the outbreak in South America

text: The present work is a statistical analysis of the COVID-19 pandemic. As the number of cases worldwide overtakes one million, data reveals closed outbreaks in Hubei and South Korea, with a new slight increase in the number of infected people in the latter. Both of these countries have reached a plateau in the number of Total Confirmed Cases per Million (TCCpM) residents, suggesting a trend to be followed by other affected regions. Using Hubei's data as a basis of analysis, we have studied the spreading rate of COVID-19 and modelled the epidemic center for 10 European countries. We have also given the final TCCpM curves for Italy and Lombardia. The introduction of the α-factor allows us to analyse the different stages of the outbreak, compare the European countries amongst each other, and, finally, to confront the initial phase of the disease between Europe and South America. Methods: By dividing the TCCpM curves in multiple sections spanning short time frames we were able to fit each section to a linear model. By pairing then the angular coefficient (α factor) of each section to the total number of confirmed infections at the center of the corresponding time interval, we have analysed how the spreading rate of Covid-19 changes as more people are infected. Also, by modelling the TCCpM curves with an asymmetrical time integral of a Normal Distribution, we were able to study, by fitting progressively larger data ensembles, how the fitting parameters change as more data becomes available. Findings: The data analysis shows that the spreading rate of COVID-19 increases similarly for all countries in its early stage, but changes as the number of TCCpM in each country grows. Regarding the modelling of the TCCpM curves, we have found that the fitting parameters oscillate with time before reaching constant values. The estimation of such values allows the determination of better parameters for the model, which in turn leads to more trustworthy forecasts on the pandemic development. Interpretation: The analysis of the oscillating fitting parameters allows an early prediction of the TCC, epidemic center and standard deviation of the outbreak. The α factor and the recovered over confirmed cases ratio can be used to understand the pandemic development in each country and to compare the protective measures taken by local authorities and their impact on the spreading of the disease.


title: On the unpredictability of outcomes of immunotherapy and preventive immunization against covid-19/ О НЕПРЕДСКАЗУЕМОСТИ РЕЗУЛЬТАТОВ ИММУНОТЕРАПИИ И ИММУНОПРОФИЛАКТИКИ COVID-19

text: This article analyzes the possibility of employing immunotherapy and preventive immunization to fight COVID-19. The authors think that treatment and prevention of the infection with anti-SARS-CoV-2 antibodies can have unpredictable outcomes. Although these antibodies can neutralize virus antigens (S-proteins), they also have the ability to enhance virus entry into the host cell. The article emphasizes the importance of solid evidence of efficacy and safety for candidate anti-COVID-19 therapies and protective measures.


title: Lung disease severity, Coronary Artery Calcium, Coronary inflammation and Mortality in Coronavirus Disease 2019.

text: IMPORTANCE The in-hospital mortality rate of the coronavirus disease 2019 (COVID-19) is higher in case of myocardial injury, but the underlying mechanism is not known and might depend on pre-existing coronary artery disease (CAD), coronary inflammation or others. OBJECTIVE To determine the association of the extent of lung disease or coronary artery chest computed tomography (HRCT) variables, the Agatston coronary calcium score (CCS) and peri-coronary adipose tissue attenuation (PCAT), representing CAD and coronary inflammation, with mortality in patients with COVID-19. DESIGN Retrospective case series. SETTING Single academic institution, Parma University Hospital, Italy, between March 5, 2020 and March 15, 2020. Final follow-up: March 30, 2020. PARTICIPANTS 500 consecutive patients with suspected COVID-19 who underwent HRCT as a gatekeeper were initially selected and the subgroup with laboratory-confirmed SARS-CoV-2 infection formed the final study group. EXPOSURES SARS-CoV-2 infection by real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay of nasopharyngeal swabs. MAIN OUTCOMES AND MEASURES In-hospital mortality was the end point. Demographic, clinical, laboratory and HRCT data were collected from hospital electronic records, and HRCT features (CCS and PCAT) were measured post-hoc from HRCT images. RESULTS Among 500 patients with suspected COVID-19, 279 had laboratory-confirmed COVID-19 and formed the study group. Among them, 170 patients (61%) were discharged alive and 109 (39%) died. Comparing patients discharged alive with patients who died, the median age was 65 vs 77 (p<0.001), with males 56% vs 68% (p=0.061), prior cardiovascular disease 9% vs 24% (p=0.001), median D-dimer 723 vs 1083 ng/ml (p<0.001), median C-reactive protein 78 vs 148 mg/L (p<0.001), the mean CCS 17 vs 189 (p<0.001) and the median PCAT -76.4 HU vs -68.6 HU (p<0.001). In multivariable analysis, only age (p<0.001), D-dimer (p=0.041), C-reactive protein (p=0.002), extent of lung disease (p=0.002), and PCAT (p<0.001), remained associated with in-hospital death. CONCLUSIONS AND RELEVANCE Increased age, D-dimer, C-reactive protein and the HRCT image features of extent of lung disease and coronary inflammation by PCAT (but not the CCS) were independently associated with mortality in hospitalized COVID-19 patients. Our study suggests that higher mortality in COVID-19 may be at least partly mediated by coronary artery inflammation.


title: Whole genome identification of potential G-quadruplexes and analysis of the G-quadruplex binding domain for SARS-CoV-2

text: The Coronavirus Disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) quickly become a global public health emergency. G-quadruplex, one of the non-canonical secondary structures, has shown potential antiviral values. However, little is known about G-quadruplexes on the emerging SARS-CoV-2. Herein, we characterized the potential G-quadruplexes both in the positive and negative-sense viral stands. The identified potential G-quadruplexes exhibits similar features to the G-quadruplexes detected in the human transcriptome. Within some bat and pangolin related beta coronaviruses, the G-quartets rather than the loops are under heightened selective constraints. We also found that the SUD-like sequence is retained in the SARS-CoV-2 genome, while some other coronaviruses that can infect humans are depleted. Further analysis revealed that the SARS-CoV-2 SUD-like sequence is almost conserved among 16,466 SARS-CoV-2 samples. And the SARS-CoV-2 SUDcore-like dimer displayed similar electrostatic potential pattern to the SUD dimer. Considering the potential value of G-quadruplexes to serve as targets in antiviral strategy, we hope our fundamental research could provide new insights for the SARS-CoV-2 drug discovery.


title: Structure-based design of hepatitis C virus E2 glycoprotein improves serum binding and cross-neutralization

text: An effective vaccine for hepatitis C virus (HCV) is a major unmet need, and it requires an antigen that elicits immune responses to key conserved epitopes. Based on structures of antibodies targeting HCV envelope glycoprotein E2, we designed immunogens to modulate the structure and dynamics of E2 and favor induction of bNAbs in the context of a vaccine. These designs include a point mutation in a key conserved antigenic site to stabilize its conformation, as well as redesigns of an immunogenic region to add a new N-glycosylation site and mask it from antibody binding. Designs were experimentally characterized for binding to a panel of human monoclonal antibodies (HMAbs) and the coreceptor CD81 to confirm preservation of epitope structure and preferred antigenicity profile. Selected E2 designs were tested for immunogenicity in mice, with and without hypervariable region 1, which is an immunogenic region associated with viral escape. One of these designs showed improvement in polyclonal immune serum binding to HCV pseudoparticles and neutralization of isolates associated with antibody resistance. These results indicate that antigen optimization through structure-based design of the envelope glycoproteins is a promising route to an effective vaccine for HCV.


title: Management of mild COVID-19: Policy implications of initial experience in India

text: Objectives- Ongoing pandemic due to COVID-19 has spread across countries, surprisingly with variable clinical characteristics and outcomes. This study was aimed at describing clinical characteristics and outcomes of admitted patients with mild COVID-19 illness in the initial phase of pandemic in India. Design - Retrospective (observational ) study. Setting - COVID facilities under AIIMS, New Delhi, where, isolation facilities were designed to manage patients with mild illness and dedicated COVID ICUs was created to cater patients with moderate to severe illness. Participants - Patients aged 18 years or more, with confirmed illness were eligible for enrolment. Patients who were either asymptomatic or mildly ill at presentation were included. Patients with moderate to severe illness at admission, or incomplete clinical symptomatology records were excluded. Methods - Data regarding demographic profile, comorbidities, clinical features, hospital course, treatment, details of results of RT-PCR for SARS-CoV-2 done at baseline and at day 14, chest radiographs (wherever available) as well as laboratory parameters was obtained retrospectively from the hospital records. Main outcome measures - Final outcome was noted in terms of course of the disease, patients discharged, still admitted (at time of conclusion of study) or death. Results -Out of 231 cases included, majority were males(78.3%) with a mean age of 39.8 years. Comorbidities were present in 21.2% of patients, diabetes mellitus and hypertension being most common. The most common symptoms were dry cough(81, 35%), fever(64, 27.7%), sore throat(36, 15.6%), and dyspnoea(24, 10.4%); asymptomatic infection was noted in 108(46.8%) patients. Presence of comorbidities was an independent predictor of symptomatic disease (OR-2.66; 95% CI 1.8 to 6.53, p= 0.03). None of the patients progressed to moderate to severe COVID-19. There were no deaths in this cohort. Conclusions - Patients with mild disease at presentation had a stable disease course and therefore such cases can be managed outside hospital setting. A large proportion of patients remained asymptomatic throughout the course of infection and those with comorbidities are more likely to be symptomatic. Trial registration - Not applicable


title: Ensuring health equity during the COVID-19 pandemic: the role of public health infrastructure

text: The COVID-19 pandemic has significantly stressed public health systems around the world and exposed the gaps in health care for underserved and vulnerable populations. In the context of the social determinants of health, focusing on health system preparedness is paramount for protecting the health of all of society. Faced with old threats (e.g., re-emergence of measles), disruptive new technologies (e.g., electronic cigarettes), increased challenges (e.g. drug-resistant organisms), and new threats (e.g., the current pandemic, climate change, politicized misinformation), our health systems must be robust and resilient. The response must include those who now suffer disproportionately—the poor and the vulnerable. Current World Health Organization priorities call for infrastructures capable of detecting, monitoring, and responding to health emergencies, such as COVID-19, and the health impacts of climate change in the context of health for all. Health care infrastructure can be better prepared and more equitable if systems are strengthened by building on core competencies and following the recommendations made for leadership, stakeholder involvement, accreditation, data collection, and funding resources. Ensuring health equity in a pandemic requires robust and resilient public health infrastructure during normal times.


title: South Korea's COVID-19 Infection Status: From the Perspective of Reconfirmation after Complete Recovery

text: COVID-19 started to occur in South Korea by an inflow of the virus from abroad, when a traveler from Wuhan, China, was first confirmed on January 19th, 2020 Although South Korea reduced the number of newly confirmed cases and is on the way to stabilizing the situation with its disease prevention policies, problems remain The main issue is the reconfirmation of the virus after recovery South Korean experts believe the reconfirmed cases are caused by reactivation of the virus inside the patients' body, rather than by virus reinfection after recovery When considering reconfirmed COVID-19 cases, it is important to keep social distancing even after treating the infection Despite no cases of reconfirmed patients infecting others having been reported yet, reexamination of patients after recovery is thought to be pivotal to prevent reactivation


title: House Democrats include research dollars in latest pandemic relief package

text: By week’s end the Democrat-led U S House of Representatives hopes to approve another massive coronavirus relief package For U S scientists, the good news is that the $3 trillion spending bill (H R 6800) unveiled last night contains billions of dollars in new research funding The bad news is that the bill is only a marker for negotiations with Senate Republicans and the White House on what more the federal government should do to help the country deal with the devastating economic and health effects of the pandemic


title: Has mortality due to other causes increased during the Covid-19 pandemic? Early evidence from England and Wales

text: Background: The Covid-19 pandemic has claimed many lives in the UK and globally. The objective of this paper is to study whether the novel coronavirus has also been associated with an increase in deaths in England and Wales for those who have not contracted the disease. Reasons behind this may include avoiding visits to hospitals or GPs, and the effects of the lockdown. Methods: I used weekly ONS data on the number of deaths that did not involve covid-19 over the period 2015-2020. Simply observing trends is not sufficient as spikes in deaths may occasionally occur. I thus followed a differences-in-differences econometric approach to study whether there was a relative increase in non-covid-19 deaths during the pandemic, compared to a control. As an additional approach, an interrupted time series model was also used. Results: Results suggest that there were an additional 531 non-covid-19 deaths in England and Wales since the outbreak of the pandemic, compared to what would have otherwise been expected [diff-in-diff interaction coeff: 531.11; 95%CI: 125.65 to 936.57]. This is confirmed by the interrupted time series model. Discussion: The health effects of covid-19 do not seem to be limited only to patients suffering from the disease, as the number of deaths for those who did not contract covid-19 has also demonstrated an absolute and relative increase. Analysing the cause of death for non-covid-19 deaths will shed light upon the reasons for the increase in such deaths and will help design appropriate policy responses to save lives.


title: Emergency response plan for the neonatal intensive care unit during epidemic of 2019 novel coronavirus

text: 2019 novel coronavirus (2019-nCoV) infection has been spreading in China since December 2019 Neonates are presumably the high-risk population susceptible to 2019-nCoV due to immature immune function The neonatal intensive care unit (NICU) should be prepared for 2019-nCoV infections as far as possible The emergency response plan enables the efficient response capability of NICU During the epidemic of 2019-nCoV, the emergency response plan for the NICU should be based on the actual situation, including diagnosis, isolation, and treatment, as well as available equipment and staffing, and take into account the psychosocial needs of the families and neonatal care staff


Atypical and novel presentations of Coronavirus Disease 2019: a case series of three children


title: A Divide and Conquer Strategy against the Covid-19 Pandemic?!

text: The concern about (socio-)economic consequences of collective lockdowns in the Covid-19 pandemic calls for alternative strategies. We consider a divide and conquer strategy in which a high risk group (HRG) is put on strict isolation, whereas the remainder of the population is exposed to the virus, building up immunity against Covid-19. The question is whether this strategy may suppress the effective reproduction number below the critical value of R_eff < 1 without further lockdown once the HRG is released from isolation. While this proposal appears already rather academic, we show that R_eff < 1 can only be obtained provided that the HRG is less than ~20-30% of the total population. Hence, this strategy is likely to fail in countries with a HRG larger than the given upper bound. In addition, we argue that the maximum infection rate occurring in this strategy is likely to exceed realistic capacities of most health care systems. While the conclusion is rather negative in this regard, we emphasise that the strategy of stopping the curve at an early stage of the Covid-19 pandemic has a chance to work out. The required duration of the lockdown is estimated to be {tau} ~ 14 days/(1-R_eff) (up to some order one factor) for R_eff < 1, provided a systematic tracing strategy of new infections exists for the subsequent relaxation phase. In this context we also argue why R_eff remains the crucial parameter which needs to be accurately monitored and controlled.


The disorder of things: Quarantine unemployment, the decline of neoliberalism, and the Covid-19 lockdown crash


title: Comparison of commercial RT-PCR diagnostic kits for COVID-19

text: The final months of 2019 witnessed the emergence of a novel coronavirus in the human population. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has since spread across the globe and is posing a major burden on society. Measures taken to reduce its spread critically depend on timely and accurate identification of virus-infected individuals by the most sensitive and specific method available, i.e. real-time reverse transcriptase PCR (RT-PCR). Many commercial kits have recently become available, but their performance has not yet been independently assessed. The aim of this study was to compare basic analytical and clinical performance of selected RT-PCR kits from seven different manufacturers (Altona Diagnostics, BGI, CerTest Biotec, KH Medical, PrimerDesign, R-Biopharm AG, and Seegene). We used serial dilutions of viral RNA to establish PCR efficiency and estimate the 95% limit of detection (LOD95%). Furthermore, we ran a panel of SARS-CoV-2-positive clinical samples (n=16) for a preliminary evaluation of clinical sensitivity. Finally, we used clinical samples positive for non-coronavirus respiratory viral infections (n=6) and a panel of RNA from related human coronaviruses to evaluate assay specificity. PCR efficiency was ≥96% for all assays and the estimated LOD95% varied within a 6-fold range. Using clinical samples, we observed some variations in detection rate between kits. Importantly, none of the assays showed cross-reactivity with other respiratory (corona)viruses, except as expected for the SARS-CoV-1 E-gene. We conclude that all RT-PCR kits assessed in this study may be used for routine diagnostics of COVID-19 in patients by experienced molecular diagnostic laboratories.


title: Geographical identification of the vulnerable groups during COVID-19 crisis: the typhoon eye effect and its boundary conditions

text: Although some studies suggest the coronavirus disease (COVID-19) is associated with negative consequences on physical health, our knowledge about the detrimental effects of COVID-19 on individual mental health is still nascent. This study uses typhoon eye theory to offer insights in helping clinical psychiatrists to screen people with well-being issues during COVID-19 outbreak. We collected survey data from working adults across different geographical areas in China on 20 and 21 February 2020 during the outbreak of COVID-19. The sample contains 308 working adults, who were in various parts of China, with varying distance to the epicenter of Wuhan. The distance of individual adults to the epicenter was negatively associated with life satisfaction ({beta} = -0.235, 95% CI -0.450 to -0.020, p = 0.032). This association between distance and life satisfaction was significant only for adults who were young or had smaller family sizes. For example, the negative relationship was strongest when the individuals were in the age bracket of 20 years old (15.7%; {beta} = -0.703, 95% CI -1.098 to -0.307; p = 0.001) and single (32.3%; {beta} = -0.767, 95% CI -1.125 to -0.408; p < 0.001). Our results that well-being deteriorates by the distance from the epicenter for specific groups of people help guide mental healthcare providers towards the regions that are further away from the epicenter in the ongoing COVID-19 outbreak. Meanwhile, our results indicate the practitioners should be cautious of using typhoon eye effect for individuals who were older or had a larger family size.


Covid19: Intensive care perspective


title: Dry Ultra-Precision Machining of Tungsten Carbide with Patterned nano PCD Tool

text: Abstract Texturing on the rake face of the tool without the metal working fluid is a potential method to reduce the friction coefficient in ultra-precision machining of tungsten carbide (WC) with a diamond tool. Low friction coefficient of the patterned tool would generate less heat in the tool-work interface and improve the tool life. This paper studies the effect of texturing on the cutting performance in ultra-precision machining of WC with a nano-polycrystalline diamond (PCD) tool. Orthogonal cutting experiments were conducted to verify the cutting performance of the textured diamond tool in machining of WC. The linear patterns parallel and perpendicular to the cutting direction were fabricated on the rake face of the nano-PCD tool by using the focused ion beam process. The experimental result showed that the friction coefficient of the perpendicular patterned tool decreased by 10%. WC surface machined with the patterned tool and non-patterned tool was also analyzed and compared. Material separation at grain boundary between tungsten grains and cobalt and full detachment of tungsten grains dominantly affected the surface quality of the machined WC surface.


title: Phase transitions and hysteresis of cooperative contagion processes

text: We investigate the effects of cooperation between two interacting infectious diseases that spread and stabilize in a host population. We propose a model in which individuals that are infected with one disease are more likely to acquire the second disease, both diseases following the susceptible-infected-susceptible reaction scheme. We analyze cooperative coinfection in stochastic network models as well as the idealized, well-mixed mean field system and show that cooperative mechanisms dramatically change the nature of phase transitions compared to single disease dynamics. We show that, generically, cooperative coinfection exhibits discontinuous transitions from the disease free to high prevalence state when a critical transmission rate is crossed. Furthermore, cooperative coinfection exhibits two distinct critical points, one for outbreaks the second one for eradication that can be substantially lower. This implies that cooperative coinfection exhibits hysteresis in its response to changing effective transmission rates or equivalently the basic reproduction number. We compute these critical parameters as a function of a cooperativity coefficient in the well-mixed mean field system. We finally investigate a spatially extended version of the model and show that cooperative interactions between diseases change the general wave propagation properties of conventional spreading phenomena of single diseases. The presented work may serve as a starting and reference point for a more comprehensive understanding of interacting diseases that spread in populations.


title: Extrapulmonary Manifestations of SARS-CoV-2: A Brief Review

text: On December 30, 2019, the first reports of a group of patients with unknown etiology pneumonia appeared in Wuhan city, Hubei province, China Taking into consideration the large amount of similar nucleotide sequences between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the past epidemic coronavirus, it will be appropriate to expect that such pathogens share the same cell line tropism and systemic pathology Although several studies have, so far, identified the clinical characteristics of COVID-19 cases, there is very little knowledge on the extrapulmonary affection of SARS-CoV-2 In this review, we summarize reports of the main affected organs besides the pulmonary system such as the liver and kidneys, as well as the cardiovascular and nervous system The mechanisms of lesion remain largely unclear The approach of this investigation is to suggest multisystemic work-up in patients with SARS-CoV-2 infection, aside from its respiratory management Correspondence to: María Fernanda Osorio Pesantes, MD, School of Medicine, Universidad Espíritu Santo-Ecuador, Av Samborondón S/N, Guayaquil 092301, Ecuador E-mail: maferosorio@uees edu ec The authors have no funding or conflicts of interest to disclose Author Statement: M F O and R G V participated in writing the original draft, and review and editing This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections Copyright © 2020 Wolters Kluwer Health, Inc All rights reserved


title: Modelling for prediction of the spread and severity of COVID-19 and its association with socioeconomic factors and virus types

text: We report the development of a Weibull based Long-Short-Term-Memory approach (W-LSTM) for the prediction of COVID-19 disease. The W-LSTM model developed in this study, performs better in terms of MSE, R2 and MAPE, as compared to the previously published models, including ARIMA, LSTM and their variations. Using W-LSTM model, we have predicted the beginning and end of the current cycle of COVID-19 in several countries. Performance of the model was validated as satisfactory in 82% of the 50 test countries, while asking for prediction for 10 days beyond the period of training. Accuracy of the above prediction with days beyond training was assessed in comparison with the MAPE that the model gave with cumulative global data. The model was applied to study correlation between the growth of infection and deaths, and a number of effectors that may influence the epidemic. The model identified age groups, trade with China, air traffic, country temperature and CoV-2 virus types as the likely effectors of infection and virulence leading to deaths. The predictors likely to promote or suppress the epidemic were identified. Some of the predictors had significant effect on the shape parameters of Weibull distribution. The model can function on cloud, take inputs in real time and handle large data country wise, at low costs to make predictions dynamically. Such predictions are highly valuable in guiding policy makers, administration and health. Interactive curves generated from the W-LSTM model can be seen at http://collaboration.coraltele.com/covid2/.


title: Modeling the Epidemic Dynamics and Control of COVID-19 Outbreak in China

text: The coronavirus disease 2019 (COVID-19) is rapidly spreading over China and more than 30 countries in last two months. COVID-19 has multiple characteristics distinct from other infectious diseases, including a high infectivity during incubation, time delay between real dynamics and daily observed case numbers, and the effects from multiple quarantine and control measures. We develop a model SUQC to adequately characterizes the dynamics of COVID-19 and explicitly model the control by artificial measures, which is more suitable for analysis than other existing epidemic models. The SUQC model is applied to the daily released data of the confirmed infected to analyze the outbreak of COVID-19 in Wuhan, Hubei (excluding Wuhan), China (excluding Hubei) and four first-tier cities of China. We find that, before January 30, 2020, all these regions except Beijing have a reproductive number R>1, and after January 30, all regions have a reproductive number R<1, indicating the effectiveness of the quarantine and control measures in inhibiting COVID-19. The confirmation rate of Wuhan is 0.0643, significantly lower than 0.1914 of Hubei (excluding Wuhan) and 0.2189 of China (excluding Hubei), but increases to 0.3229 after Feb 12th when clinical diagnosis was adopted. The un-quarantined infected individuals in Wuhan on February 12, 2020 is as high as 3,509 and decreases to 334 on February 21th, 2020. After fitting the model with recent data, we predict that the end times of COVID-19 of Wuhan and Hubei are around late-March, of China (excluding Hubei) around mid-March, and of the four tier-one cities before March 2020. A total of 80,511 individuals of the whole country are infected, among which 49,510 are from Wuhan, 17,679 from Hubei(excluding Wuhan), and the rest 13,322 from other regions of China (excluding Hubei). We suggest the rigorous quarantine and control measures should be kept before March in Beijing, Shanghai, Guangzhou and Shenzhen, and before late-March in Hubei. The model can also be useful to predict the trend of epidemic and provide quantitative guide for other counties in a high risk of outbreak, such as South Korea, Japan and Iran.