title: Trajectories of depressive symptoms among vulnerable groups in the UK during the COVID-19 pandemic

text: Objective: The coronavirus disease 2019 (COVID-19) pandemic has affected many aspects of the human condition, including mental health and psychological wellbeing. This study examined trajectories of depressive symptoms (DST) over time among vulnerable individuals in the UK during the COVID-19 pandemic. Methods: The sample consisted of 51,417 adults recruited from the COVID-19 Social Study. Depressive symptoms were measured on seven occasions (21st March - 2nd April), using the Patient Health Questionnaire (PHQ-9). Sociodemographic vulnerabilities included non-white ethnic background, low socio-economic position (SEP), and type of work (keyworker versus no keyworker). Health-related and psychosocial vulnerabilities included pre-existing physical and mental health conditions, experience of psychological and/or physical abuse, and low social support. Group-based DST were derived using latent growth mixture modelling and multivariate logistic regression models were fitted to examine the association between these vulnerabilities and DSTs. Model estimates were adjusted for age, sex, and suspected COVID-19 diagnosis. Results: Three DSTs were identified: low [N=30,850 (60%)] moderate [N=14,911 (29%)], and severe [N=5,656 (11%)] depressive symptoms. DSTs were relatively stable across the first 6 weeks of lockdown. After adjusting for covariates, experiences of physical/psychological abuse (OR 13.16, 95% CI 12.95-13.37), pre-existing mental health conditions (OR 13.00 95% CI 12.87-13.109), pre-existing physical health conditions (OR 3.41, 95% CI 3.29-3.54), low social support (OR 12.72, 95% CI 12.57-12.86), and low SEP (OR 5.22, 95% CI 5.08-5.36) were significantly associated with the severe DST. No significant association was found for ethnicity (OR 1.07, 95% 0.85-1.28). Participants with key worker roles were less likely to experience severe depressive symptoms (OR 0.66, 95% 0.53-0.80). Similar but smaller patterns of associations were found for the moderate DST. Conclusions: People with psychosocial and health-related risk factors, as well as those with low SEP seem to be most vulnerable to experiencing moderate or severe depressive symptoms during the COVID-19 pandemic.


title: Nitric oxide gas inhalation to prevent COVID-2019 in healthcare providers

text: Introduction: In human hosts, SARS-CoV-2 causes a respiratory syndrome (named COVID-19) which can range from a mild involvement of the upper airways to a severe pneumonia with acute respiratory syndrome that requires mechanical ventilation in an intensive care unit (ICU). Hospital-associated transmission is an important route of spreading for the SARS-CoV-2 virus and healthcare providers are at the highest risk. As of February 2020, 1716, Chinese healthcare workers had confirmed SARS-CoV-2 infections and at least 6 died. Unfortunately, there is currently no vaccine or pharmacological prophylaxis to decrease the risk of healthcare providers contracting the infection. Methods and analysis. We will randomize 470 healthcare providers scheduled to work with COVID 19 patients to receive nitric oxide gas administration (NO group, n=235) or no gas administration (control group, n=235). The primary endpoint of this study is the incidence of subjects with COVID-19 disease at 14 days from enrollment. Secondary endpoints are the proportion of healthcare providers who present a positive real time RT-PCR test for SARS-CoV-2 14 days after enrollment, the proportion of healthcare providers requiring quarantine, and the total number of quarantine days in the two groups. Ethics and dissemination. The trial protocol is under the approval of The Partners Human Research Committee of Massachusetts General Hospital (Boston, USA) and recruitment is expected to start in April 2020. The results of this study will be published in scientific journals and presented at scientific meetings.


title: Multiple expression assessments of ACE2 and TMPRSS2 SARS-CoV-2 entry molecules in the urinary tract and their associations with clinical manifestations of COVID-19

text: Background Since December 2019, the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first spread quickly in Wuhan, China, then globally. From previously published evidence, ACE2 and TMPRSS2, are both pivotal entry molecules that enable cellular infection by SARS-CoV-2. Meanwhile, increased expression of pro-inflammatory cytokines, or a “cytokine storm,” is associated with multiple organ dysfunction syndrome that is often observed in critically ill patients. Methods We investigated the expression pattern of ACE2 and TMPRSS2 in major organs in the human body, especially under specific disease conditions. Multiple sequence alignment of ACE2 in different species was used to explain animal susceptibility. Moreover, the cell-specific expression patterns of ACE2 and cytokine receptors in the urinary tract were assessed using single-cell RNA sequencing (scRNA-seq). Additional biological relevance was determined through Gene Set Enrichment Analysis (GSEA) using an ACE2 specific signature. Results Our results revealed that ACE2 and TMPRSS2 were highly expressed in genitourinary organs. ACE2 was highly and significantly expressed in the kidney among individuals with chronic kidney diseases or diabetic nephropathy. In single cells, ACE2 was primarily enriched in gametocytes in the testis, and renal proximal tubules. The receptors for pro-inflammatory cytokines, especially IL6ST, were remarkably concentrated in endothelial cells, macrophages, and spermatogonial stem cells in the testis, and renal endothelial cells, which suggested the occurrence of alternative damaging mechanisms via autoimmune attacks. Conclusions This study provided new insights into the pathogenicity mechanisms of SARS-CoV-2 that underlie the clinical manifestations observed in the human testis and kidney. These observations might substantially facilitate the development of effective treatments for this rapidly spreading disease.


title: Social Media Platforms for Health Communication and Research in the Face of COVID-19 Pandemic: A Cross Sectional Survey in Uganda.

text: Objectives: (1) To examine the usage of social media and other forms of media among medical students (MS) and healthcare professionals (HCPs) in Uganda. (2) To assess the perceived usefulness of social media and other forms of media for COVID-19 public health campaigns. Design: A descriptive WhatsApp messenger-based cross-sectional survey in April 2020. Setting: Makerere University Teaching Hospitals (MUTH) and 9 of the 10 medical schools in Uganda. Participants: HCPs at MUTH and MS in the 9 medical schools in Uganda. Main outcome measures: We collected data on sociodemographic characteristics, sources of information on COVID-19, preferences of social media platform and perceived usefulness of the different media platforms for acquisition of knowledge on COVID-19. Results: Overall, response rate was 21.5% for both MS and HCPs. In total, 877 (HCPS [136, 15.5%], MS [741, 85.5%]) were studied. Majority (n=555, 63.3%) were male with a median age of 24 (range: 18-66) years. Social media was a source of information for 665 (75.8%) participants. Usage was similar among MS and HCPs (565/741 (76.2%) vs. 100/136 (73.5%), p=0.5). Among the MS, commonly used social media were: WhatsApp (n=705, 95.1%) Facebook (n=405, 54.8%), Twitter (n=290, 39.1%), Instagram (n=178, 24.0) and Telegram (n=80, 10.8%). Except for WhatsApp, male MS we more likely to use the other social media platforms (p= <0.001 to 0.01). Mass media (television and radio) and social media were preferred the most useful tools for dissemination of COVID-19 related information. Conclusion: More than two-thirds of MS and HCPs are routinely using social media in Uganda. Social media platforms may be used for dissemination of information as well as a research tool among MS and HCPs. Social media alongside other media platforms can also be used as sources of reliable information on COVID-19 as well as for dissemination of research findings and guidelines.


docid: fqhyxejw

title: Prognostic factors for severity and mortality in patients infected with COVID-19: A living systematic review protocol

text: Objective The objective of our systematic review is to identify prognostic factors that can potentially be used in decision-making related to the care of patients infected with COVID-19. Design This is the protocol of a living systematic review. Data sources We will conduct searches in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), grey literature and in a centralised repository in L-OVE (Living OVerview of Evidence). L-OVE is a platform that maps PICO questions to evidence from Epistemonikos database. In response to the COVID-19 emergency, L-OVE was adapted to expand the range of evidence it covers and customised to group all COVID-19 evidence in one place. The search will cover the period until the day before submission to a journal. Eligibility criteria for selecting studies and methods We will follow a common protocol for multiple parallel systematic reviews, already published and submitted to PROSPERO (awaiting ID allocation). We will include studies that assess patients with confirmed or suspected infection with SARS-CoV-2 and inform the relation of potential prognostic factors with death or disease severity. Two groups of two reviewers will independently screen studies for eligibility, extract data, and assess the risk of bias. We will perform meta-analyses and use GRADE to assess the certainty of evidence for each prognostic factor and outcome. A living, web-based version of this review will be openly available during the COVID-19 pandemic. We will resubmit it if the conclusions change or there are substantial updates. Ethics and dissemination No ethics approval is considered necessary. The results of this review will be widely disseminated via peer-reviewed publications, social networks and traditional media.


title: Impact of the Novel Coronavirus Disease (COVID-19) on Treatment Adherence and Sleep Duration in Obstructive Sleep Apnea Patients Treated with Positive Airway Pressure

text: Objective To examine the effect of COVID-19 on treatment adherence and self-reported sleep duration among patients with Obstructive Sleep Apnea (OSA) treated with positive airway pressure (PAP) therapy. Methods Retrospective review of medical records of patients seen in Sleep and Circadian Clinic at Brigham Health during the immediate period of one month after the national lockdown was announced on March 15, 2020. Patients with OSA were included only if PAP adherence data was available in the 12- months prior and in the month after the lockdown. Patients with other sleep disorders and OSA patients without the adherence data were excluded. Results Mean age was 63.5 +/- 13.9 years, 55% of the participants were men, and mean BMI was 31.8 +/- 7.9 kg/m2. Severe OSA was noted among 59.5% compared to 29.3% moderate, and 11.2% mild OSA. Increased number of patients reported insomnia after the lockdown (41% vs 48%, p= 0.02). Gender stratification noted worsening insomnia only among women. There was no significant difference in PAP adherence as measured by the hours of use, self-reported sleep duration or in the use of sleep medications. Conclusion Post COVID-19 lockdown had a negative impact on sleep as evidenced by increased reporting of insomnia particularly among women, but no impact on PAP adherence or self-reported sleep duration.


title: Impact of COVID-19 on orthopaedic care: a call for nonoperative management

text: BACKGROUND: Surgical specialties face unique challenges caused by SARS-COV-2 (COVID-19). These disruptions will call on clinicians to have greater consideration for non-operative treatment options to help manage patient symptoms and provide therapeutic care in lieu of the traditional surgical management course of action. This study aimed to summarize the current guidance on elective surgery during the COVID-19 pandemic, assess how this guidance may impact orthopaedic care, and review any recommendations for non-operative management in light of elective surgery disruptions. METHODS: A systematic search was conducted, and included guidance were categorized as either “Selective Postponement” or “Complete Postponement” of elective surgery. Selective postponement was considered as guidance that suggested elective cases should be evaluated on a case-by-case basis, whereas complete postponement suggested that all elective procedures be postponed until after the pandemic, with no case-by-case consideration. In addition, any statements regarding conservative/non-operative management were summarized when provided by included reports. RESULTS: A total of 11 reports from nine different health organizations were included in this review. There were seven (63.6%) guidance reports that suggested a complete postponement of non-elective surgical procedures, whereas four (36.4%) reports suggested the use of selective postponement of these procedures. The guidance trends shifted from selective to complete elective surgery postponement occurred throughout the month of March. The general guidance provided by these reports was to have an increased consideration for non-operative treatment options whenever possible and safe. As elective surgery begins to re-open, non-operative management will play a key role in managing the surgical backlog caused by the elective surgery shutdown. CONCLUSION: Global guidance from major medical associations are in agreement that elective surgical procedures require postponement in order to minimize the risk of COVID-19 spread, as well as increase available hospital resources for managing the influx of COVID-19 patients. It is imperative that clinicians and patients consider non-operative, conservative treatment options in order to manage conditions and symptoms until surgical management options become available again, and to manage the increased surgical waitlists caused by the elective surgery shutdowns.


title: Country differences in hospitalisation, length of stay and admission to Intensive Care Units due to SARS-CoV-2 infection: a rapid review of available literature

text: Objectives: Coronavirus disease (COVID-19) caused by the SARS-CoV-2 virus is spreading rapidly worldwise and threatening the collapse of national health care systems. The development of effective resource models are critical for long term health planning. The aim was to evaluate the available literature, to consider parameters affecting hospital resources, to effectively guide health policy and planning. Design: A detailed search of the literature, using Google Scholar, PubMED, MedRxiv and BioRxiv, was conducted for the time period 01-DEC-2019 to 04-MAY-2020; using appropriate keywords: resultant articles were scrutinised in detail, and appraised for reported data pertaining to hospitalization and hospital length of stay (LOS). Results: Disease presentation was described in China; 81 % mild, 14 % moderate and 5 % severe. The experience, thus far, in Europe and the USA are suggestive of a higher degree of severity. Initial reports suggest high hospitalisation and ICU admittance rates. More recent reports from the ECDC lower this estimation. Perhaps the relative age, the level of pre-existing conditions, and other health factors may be contributors to differences. Data from Irish cases suggest hospitalisation rate may be lower in parts of Europe and time dependent. Hospital LOS is described in seventeen articles, with median lengths of stay between 4 and 25 days. The evidence regarding the LOS in ICU is reported in eighteen studies, fifteen deemed relevant. The majority of studies report ICU LOS between 7 to 10 days. Many of these studies are likely skewed towards shorter stay due to study cut-off dates. Indications based on ICU LOS reported for patients continuing care suggest median ICU stay will be longer. Conclusions: These parameter estimates are key to the development of an effective health care resource model. Based on our rapid appraisal of the literature, is it essential that Europe manages mitigation measures to ensure that hospital and ICU capacity does not become overwhelmed to manage this pandemic long term.


title: Estimating the true (population) infection rate for COVID-19: A Backcasting Approach with Monte Carlo Methods

text: Differences in COVID-19 testing and tracing across countries, as well as changes in testing within each country over time, make it difficult to estimate the true (population) infection rate based on the confirmed number of cases obtained through RNA viral testing. We applied a backcasting approach, coupled with Monte Carlo methods, to estimate a distribution for the true (population) cumulative number of infections (infected and recovered) for 15 countries where reliable data are available. We find a positive relationship between the testing rate per 1,000 people and the implied true detection rate of COVID-19, and a negative relationship between the proportion who test positive and the implied true detection rate. Our estimates suggest that the true number of people infected across our sample of 15 developed countries is 18.2 (5-95% CI: 11.9-39.0) times greater than the reported number of cases. In individual countries, the true number of cases exceeds the reported figure by factors that range from 1.7 (5-95% CI: 1.1-3.6) for Australia to 35.6 (5-95% CI: 23.2-76.3) for Belgium.


title: Structural insight into the putative role of novel SARS CoV-2 E protein in viral infection: a potential target for LAV development and therapeutic strategies

text: The outbreak of COVID-19 across the world has posed unprecedented and global challenges on multiple fronts. Most of the vaccine and drug development has focused on the spike proteins and viral RNA-polymerases. Using the bioinformatics and structural modeling approach, we modeled the structure of the envelope (E)-protein of novel SARS-CoV-2. The E-protein of this virus shares sequence similarity with that of SARS-CoV-1, and is highly conserved in the N-terminal regions. Incidentally, compared to spike proteins, E proteins demonstrate lower disparity and mutability among the isolated sequences. Using homology modeling, we found that the most favorable structure could function as a gated proton channel. Combining pocket estimation and docking with water, we determined that GLU 8 and ASN 15 in the N-terminal region were in close proximity to form H-bonds. Additionally, two distinct “core” structures were visible, the hydrophobic core and the central core, which may regulate the opening/closing of the channel. We propose this as a mechanism of viral proton channeling activity which may play a critical role in viral infection. In addition, it provides a structural basis and additional avenues for LAV development and generating therapeutic interventions against the virus. Significance Statement Structural modeling of the novel SARS-CoV-2 envelope protein (E-protein) demonstrating its possible proton channeling activity


docid: thwnmobo

title: Companion vaccine Bioinformatic design tool reveals limited functional genomic variability of SARS-Cov-2 Spike Receptor Binding Domain

text: Tracking the genetic variability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for several reasons, such as to identify target sequences to generate robust vaccines and neutralizing monoclonal antibodies; to track viral genetic temporal and geographic evolution; and to mine for viral variants associated with reduced or increased severity. Several online tools and bioinformatic analyses have been released for this purpose; four main viral clades have been described via phylogenetic analyses. Here, we present an open-source bioinformatic protocol focused on SARS-CoV-2 single mutations and minimal consensus sequence building as a companion vaccine design tool. Results on the whole GISAID sequence dataset at the time of the writing (April–June 2020) confirms no high variability pressure on the viral genome in terms of quality and quantity of mutations. We then focused our analysis on the receptor-binding domain region of the spike protein and only found a few variants associated with particular geographic locations that should be tracked over time. Finally, additional immunogenomic analyses revealed some variation in mutated epitope MHC compatibility and T-cell recognition for most frequent human HLAs.


title: Artificial intelligence driven assessment of routinely collected healthcare data is an effective screening test for COVID-19 in patients presenting to hospital

text: The early clinical course of SARS-CoV-2 infection can be difficult to distinguish from other undifferentiated medical presentations to hospital, however viral specific real- time polymerase chain reaction (RT-PCR) testing has limited sensitivity and can take up to 48 hours for operational reasons. In this study, we develop two early-detection models to identify COVID-19 using routinely collected data typically available within one hour (laboratory tests, blood gas and vital signs) during 115,394 emergency presentations and 72,310 admissions to hospital. Our emergency department (ED) model achieved 77.4% sensitivity and 95.7% specificity (AUROC 0.939) for COVID- 19 amongst all patients attending hospital, and Admissions model achieved 77.4% sensitivity and 94.8% specificity (AUROC 0.940) for the subset admitted to hospital. Both models achieve high negative predictive values (>99%) across a range of prevalences (<5%), facilitating rapid exclusion during triage to guide infection control. We prospectively validated our models across all patients presenting and admitted to a large UK teaching hospital group in a two-week test period, achieving 92.3% (n= 3,326, NPV: 97.6%, AUROC: 0.881) and 92.5% accuracy (n=1,715, NPV: 97.7%, AUROC: 0.871) in comparison to RT-PCR results. Sensitivity analyses to account for uncertainty in negative PCR results improves apparent accuracy (95.1% and 94.1%) and NPV (99.0% and 98.5%). Our artificial intelligence models perform effectively as a screening test for COVID-19 in emergency departments and hospital admission units, offering high impact in settings where rapid testing is unavailable.


title: Takotsubo Syndrome Associated with COVID-19

text: OBJECTIVE: The availability of public health information for optimised supportive care is critical during the COVID-19 pandemic. We describe the first case of COVID-19 complicated by Takotsubo cardiomyopathy. MATERIALS AND METHODS: We report the clinical, laboratory and radiological findings of a patient with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RESULTS: The nasopharyngeal swab was positive for SARS-CoV-2 and x-ray images demonstrated pathognomonic pneumonia. The patient developed tachycardia and the echocardiogram confirmed the diagnosis of Takotsubo cardiomyopathy. CONCLUSIONS: Doctors should be aware of the need to thoroughly study this new infection in order to understand its underlying mechanisms and related complications. LEARNING POINTS: We report the first case of Takotsubo cardiomyopathy associated with COVID-19. We discuss a rare presentation in the current pandemic. COVID-19 can be associated with cardiac complications, even after the onset of pneumonia, and so strict monitoring of these patients is essential.


title: The immediate psychological response of the general population in Saudi Arabia during COVID-19 pandemic: a cross-sectional study

text: Background: The health and economic burden pandemic diseases significantly cause psychosocial problems. The outbreak of COVID-19 may differentially exacerbate anxiety and stress in people subjected to the real or perceived threat of the virus. Method: An online cross-sectional survey was carried out to assess the general population's immediate psychological response during the initial state of the outbreak in Saudi Arabia. The study used brief screening tools PHQ-4 for anxiety-depression symptoms and IES-6 for posttraumatic stress disorder symptoms. Results: Among the 584 respondents, 19.8% and 22.0% reported moderate to severe anxiety and depression symptoms, respectively. According to the combined PHQ-4 score, 14.5% of participants showed moderate to severe anxiety or depression disorder. 64.8% met the level of clinical concern for posttraumatic stress disorder, and 51.3% met the level of probable posttraumatic stress disorder diagnosis. Multivariate analyses showed that females, non-Saudi nationalities, and those who had mental illness history were more vulnerable to anxiety and depression disorders than their counterparts, whereas a higher prevalence of distress symptoms was reported among those who prefer Arabic over English for communication. It was found that people whose colleagues or family infected with the disease were more likely to report moderate to severe symptoms of anxiety or depression and distress. The study further showed that the higher the perceived threat, the higher the chances of exhibiting anxiety-depressive disorder symptoms and distress symptoms. Conclusion: The findings are a matter for serious concern, and considerable attention is required from authorities and policymakers regarding early detection and treatment of these illnesses in order to reduce the burden of the pandemic related mental illness.


title: MATHEMATICAL MODELING FOR TRANSMISSIBILITY OF COVID-19 VIA MOTORCYCLES

text: In this paper, we present a mathematical model of trigonometric type for transmissibility and deaths as a result of COVID-19. In the model, we analyze the spread of COVID-19 by considering a new parameter, the motorcycle as a means of public transport, which has not been considered in several other models for COVID-19. We use the mathematical model to predict the spread and deaths and we suggest strategies that can be put in place to prevent the spread caused by motorcycle as a means of public transport.


COVID-19: Neurology Instructors Rethink Medical Clerkship Training as Clinical Rotations Are on Pause


title: Sample-Efficient Deep Learning for COVID-19 Diagnosis Based on CT Scans

text: Coronavirus disease 2019 (COVID-19) has infected more than 1.3 million individuals all over the world and caused more than 106,000 deaths. One major hurdle in controlling the spreading of this disease is the inefficiency and shortage of medical tests. There have been increasing efforts on developing deep learning methods to diagnose COVID-19 based on CT scans. However, these works are difficult to reproduce and adopt since the CT data used in their studies are not publicly available. Besides, these works require a large number of CTs to train accurate diagnosis models, which are difficult to obtain. In this paper, we aim to address these two problems. We build a publicly-available dataset containing hundreds of CT scans positive for COVID-19 and develop sample-efficient deep learning methods that can achieve high diagnosis accuracy of COVID-19 from CT scans even when the number of training CT images are limited. Specifically, we propose an Self-Trans approach, which synergistically integrates contrastive self-supervised learning with transfer learning to learn powerful and unbiased feature representations for reducing the risk of overfitting. Extensive experiments demonstrate the superior performance of our proposed Self-Trans approach compared with several state-of-the-art baselines. Our approach achieves an F1 of 0.85 and an AUC of 0.94 in diagnosing COVID-19 from CT scans, even though the number of training CTs is just a few hundred.


docid: vkphgilw

title: Near- and forecasting the SARS-COV-2 epidemic requires a global view and multiple methods

text: Conventional epidemiological models require estimates of important parameters including incubation time and case fatality rate that may be unavailable in the early stage of an epidemic. For the ongoing SARS-COV-2 epidemic, with no previous population exposure, alternative prediction methods less reliant on assumptions may prove more effective in the near-term. We present three methods used to provide early estimates of likely SARS-COV-2 epidemic progression. During the first stage of the epidemic, growth rate charts revealed the UK, Italy and Spain as outliers, with differentially increasing growth of deaths over cases. A novel data-driven time-series model was then used to near-cast 7-day future cases and deaths with much greater precision. Finally, an epidemio-statistical model was used to bridge from near-casting to forecasting the future course of the global epidemic. By applying multiple approaches to global SARS-COV-2 data, coupled with mixed-effects methods, countries further ahead in the epidemic provide valuable information for those behind. Using current daily global data, we note convergence in near-term predictions for Italy signifying an appropriate call on the future course of the global epidemic. For the UK and elsewhere, prediction of peak and eventual time to resolution is now possible.


title: Comorbid Diabetes Mellitus was Associated with Poorer Prognosis in Patients with COVID-19: A Retrospective Cohort Study

text: Background The 2019 novel coronavirus disease (COVID-19) emerged in Wuhan, Hubei province, China, and was characterized as pandemic by the World Health Organization. Diabetes mellitus is an established risk factor for poor clinical outcomes, but the association of diabetes with the prognosis of COVID-19 have not been reported yet. Methods In this cohort study, we retrospectively reviewed 258 consecutive hospitalized COVID-19 patients with or without diabetes at the West Court of Union Hospital of Huazhong University of Science and Technology in Wuhan, China, recruited from January 29 to February 12, 2020. The cases were confirmed by real-time PCR and the demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Prognosis was defined as hospitalization, discharged survivor and death, which was followed up until March 12, 2020. Results Of the 258 hospitalized patients (63 with diabetes) with COVID-19, the median age was 64 years (range 23-91), and 138 (53.5%) were male. No significant differences in age and sex were identified between patients with and without diabetes. Common symptoms included fever (82.2%), dry cough (67.1%), polypnea (48.1%), and fatigue (38%). Patients with diabetes had significantly higher leucocyte and neutrophil counts, and higher levels of fasting blood glucose, serum creatinine, urea nitrogen and creatine kinase isoenzyme MB at admission compared with those without diabetes. COVID-19 patients with diabetes were more likely to develop severe or critical disease condition with more complications at presentation, and had higher incidence rates of antibiotic therapy, non-invasive and invasive mechanical ventilation, and death (11.1% vs. 4.1%). Cox proportional hazard model showed that diabetes (adjusted hazard ratio [aHR]=3.64; 95% confidence interval [CI]: 1.09, 12.21) and fasting blood glucose (aHR=1.19; 95% CI: 1.08, 1.31) were associated with the fatality of COVID-19, adjusting for potential confounders. Conclusions Diabetes mellitus is associated with greater disease severity and a higher risk of mortality in patients with COVID-19. Primary and secondary prevention strategies are needed for COVID-19 patients with diabetes.


title: Eat, Pray, Work: A meta-analysis of COVID-19 Transmission Risk in Common Activities of Work and Leisure

text: ABSTRACT. BACKGROUND. When the lockdowns are relaxed, the responsibility of mitigating the COVID-19 spread shifts from the governments to the individuals. To know how to conduct one-self, it is important for everyone to know the risks of transmission during the quotidian activities - meetings, meals, etc, from individuals who are known to them and looking healthy. METHODS. The detailed case-studies corresponding to 425 infections upon point-exposures over a specified duration are curated. The data from the case studies is summarized and reorganized to reflect different situations from the daily life. A meta-analysis of the attack rates of transmission and the number of infections per infected person are performed. RESULTS. The attack rates are very high in family dinners (66.7% (48.8-80.8%)) compared to sit-down dinners with lesser mixing among people eating at different tables (15.7% (12.1-20.1%)), both lasting a couple of hours. In an open workspace office floor organized in a two-half structure with shared elevators and restrooms and the employees speaking continuously, the average attack rate over the course of a few days was much higher in one half (78.7% (70.3-85.3%)) than the one for the entire floor (43.5% (37.0-50.1%)). Inferred data suggests that the transmission in elevators and trains may be lower under the conditions of using masks. In most of the instances we studied, the infected individuals spreading (35/44) and even super-spreading (3/6) were mostly without symptoms of coughing, sneezing or a fever. CONCLUSIONS. Although the basic reproduction number R0 is around 3.0, the number of infections caused, including the super-spreading events, seem to be limited by the number of personal interactions in a group and their proximity. By acknowledging the risks in daily life, from healthy-looking persons, one may be able to organize their interactions better to reduce the chances of spreading or super-spreading infections.


title: Mathematical Model to Study Early COVID-19 Transmission Dynamics in Sri Lanka

text: Background: World Health Organization declared COVID-19 as a pandemic on 11th March. Sri Lanka is currently experiencing a cluster epidemic with a specific group of overseas returnees and their contacts. The objective of this study was to develop a mathematical model to predict the epidemic in Sri Lanka incorporating measures taken for social distancing and prevention of social gatherings. Methods: A hybrid model incorporating both exponential and polynomial features was developed and parameters were estimated. The developed model was validated using the datasets of three reference countries. Finally, the model was applied to the Sri Lankan data to simulate the epidemic behaviour. Additional features were incorporated to the model to examine the effects of current control measures. Findings: Sri Lanka will have a peak of 177 COVID-19 active cases at the end of second incubation period from the index case of our projection, if the same trend continues. At 10% risk, we project a peak of 263 COVID-19 active cases at the end of third incubation period, and a peak of 353 at the end of fourth incubation period. Should the risk level reach 20%, the peak will be above 1000 active cases after 90 days. Simulations incorporating control measures predict that, deviation from the control measures currently in place could trigger exponential behaviour of the epidemic. Interpretation: The hybrid model combining exponential and polynomial functions showed promising results to predict COVID-19 epidemic. Projections indicate that any early relaxation of control measures is not advisable. This methodological approach can be replicated in other settings at the initial stages of the epidemic.


title: Assessment of the outbreak risk, mapping and infestation behavior of COVID-19: Application of the autoregressive and moving average (ARMA) and polynomial models

text: Infectious disease outbreaks pose a significant threat to human health worldwide. The outbreak of pandemic coronavirus disease 2019 (COVID 2019) has caused a global health emergency. Identification of regions with high risk for COVID 19 outbreak is a major priority of the governmental organizations and epidemiologists worldwide. The aims of the present study were to analyze the risk factors of coronavirus outbreak and identify areas with a high risk of human infection with virus in Fars Province, Iran. A geographic information system (GIS) based machine learning algorithm (MLA), support vector machine (SVM), was used for the assessment of the outbreak risk of COVID 19 in Fars Province, Iran. The daily observations of infected cases was tested in the third-degree polynomial and the autoregressive and moving average (ARMA) models to examine the patterns of virus infestation in the province and in Iran. The results of disease outbreak in Iran were compared with the data for Iran and the world. Sixteen effective factors including minimum temperature of coldest month (MTCM), maximum temperature of warmest month (MTWM), precipitation in wettest month (PWM), precipitation of driest month (PDM), distance from roads, distance from mosques, distance from hospitals, distance from fuel stations, human footprint, density of cities, distance from bus stations, distance from banks, distance from bakeries, distance from attraction sites, distance from automated teller machines (ATMs), and density of villages were selected for spatial modelling. The predictive ability of an SVM model was assessed using the receiver operator characteristic area under the curve (ROC AUC) validation technique. The validation outcome reveals that SVM achieved an AUC value of 0.786 (March 20), 0.799 (March 29), and 86.6 (April 10) a good prediction of change detection. The growth rate (GR) average for active cases in Fars for a period of 41 days was 1.26, whilst it was 1.13 in country and the world. The results of the third-degree polynomial and ARMA models revealed an increasing trend for GR with an evidence of turning, demonstrating extensive quarantines has been effective. The general trends of virus infestation in Iran and Fars Province were similar, although an explosive growth of the infected cases is expected in the country. The results of this study might assist better programming COVID 19 disease prevention and control and gaining sorts of predictive capability would have wide ranging benefits.


title: Primary application of disposable portable gastroscopy in emergency upper gastrointestinal examination/ 便携式一次性电子胃镜在急诊上消化道检查中的初步应用

text: Objective To provide a portable disposable endoscopy for preventing potential viral infection in the patients with acute upper gastrointestinal bleeding (AUGIB) or those who need emergency endoscopy and reducing the process of endoscopy cleaning and disinfection during the corona virus disease 2019 (COVID-19) epidemic. Methods The novel portable and disposable endoscopy system (YunSendo) was self-designed. Two patients with suspected AUGIB underwent emergency gastroscopy with YunSendo system by a senior endoscopist. Standard image acquisition and assessments of operation performance and image quality were fulfilled to evaluate the preliminary safety, feasibility, and operation performance of the novel endoscopy. Results Emergency endoscopy was completed safely in two AUGIB patients by the YunSendo system without alternating current (AC) power supply. The endoscopic manipulation and observation, including water absorption, air inflation, water spray, body rotation, and specimen biopsy, can be smoothly and effectively achieved. The video-recording, image acquisition, and electronic graphic report output were achieved integratedly in YunSendo. The upper GI tract can be clearly visualized, with eligible specimen biopsy without any obvious adverse events and compilations. Operation time was similar to an ordinary gastroscopy. The disposable endoscope was discarded after use according to the requirements of the hospital infection-control department. Conclusions The novel portable and disposable endoscopy system, YunSendo, is safe and feasible for upper gastrointestinal examination, with favorable operation performance and image quality. The preliminary experience provides evidence for its convenient use of epidemic prevention.


title: Anosmia and Dysgeusia in the Absence of Other Respiratory Diseases: Should COVID-19 Infection Be Considered?

text: We describe two elderly patients evaluated at emergency departments for anosmia/dysgeusia in the absence of any other respiratory symptoms prior to or upon admission. In the current epidemiological context, clinical and biological work-up led to a diagnosis of COVID-19 infection. Unfortunately, one of the patients died during hospitalization, but the other recovered and was discharged. LEARNING POINTS: In the current epidemiological situation, anosmia and dysgeusia in the absence of other respiratory conditions should be carefully evaluated. Special attention should be given to patients with non-classic COVID-19 symptoms in order to reduce transmission and protect health providers.


title: Scaling up remdesivir amid the coronavirus crisis

text: With society clamoring for something—anything—that can stem the rapidly rising death toll of the COVID-19 pandemic, Gilead Sciences’ antiviral remdesivir has emerged as a closely watched treatment option Laboratory studies of other coronaviruses suggested the drug might be able to take down this new one, which causes COVID-19 As the outbreak took hold in China in January, it was among the first treatments that doctors tried Now, with cases worldwide at more than 3 million, scrutiny of data coming out of clinical trials of the drug has reached fever pitch When the health-focused news site Stat posted a story based on a leaked video of a University of Chicago clinician talking optimistically about remdesivir’s possible effectiveness, it didn’t just prop up Gilead’s stock price;it lifted the entire stock market With each new anecdote, whether about an individual patient or a hunch from a doctor running a trial, the pressure View: PDF ;Full Text HTML


title: Elevated D-Dimer Levels are Associated with Increased Risk of Mortality in COVID-19: A Systematic Review and Meta-Analysis

text: Introduction. The 2019 novel Coronavirus (2019 nCoV), now declared a pandemic has an overall case fatality of 2 to 3% but it is as high as 50% in critically ill patients. D-dimer is an important prognostic tool, often elevated in patients with severe COVID-19 infection and in those who suffered death. In this systematic review, we aimed to investigate the prognostic role of D-dimer in COVID-19 infected patients. Methods. We searched PubMed, Medline, Embase, Ovid, and Cochrane for studies reporting admission D-dimer levels in COVID-19 patients and its effect on mortality. Results. 18 studies (16 retrospective and 2 prospective) with a total of 3,682 patients met the inclusion criteria. The pooled mean difference (MD) suggested significantly elevated D-dimer levels in patients who died versus those survived (MD 6.13 mg/L, 95% CI 4.16 to 8.11, p <0.001). Similarly, the pooled mean D-dimer levels were significantly elevated in patients with severe COVID-19 infection (MD 0.54 mg/L, 95% CI 0.28 to 0.8, p< 0.001). In addition, the risk of mortality was four-fold higher in patients with positive D-dimer vs negative D-dimer (RR 4.11, 95% CI 2.48 to 6.84, p< 0.001) and the risk of developing the severe disease was two-fold higher in patients with positive D-dimer levels vs negative D-dimer (RR 2.04, 95% CI 1.34 to 3.11, p < 0.001). Conclusion. Our meta-analysis demonstrates that patients with COVID-19 presenting with elevated D-dimer levels have an increased risk of severe disease and mortality.


title: 40th International Congress of the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) 19-22 May 2020, Tallinn, Estonia

text: Although it was with great sadness that we had to cancel the 2020 congress, which was to have been held in Tallinn, Estonia, due to the COVID-19 pandemic, the EAPCCT Board and Scientific and Meetin


title: Retrospective Analysis of Clinical Features in 101 Death Cases with COVID-19

text: Background The illness progress of partial patient of COVID-19 is rapid and the mortality rate is high.we aim to describe the clinical features in death cases with COVID-19. Methods In this single center, observational study, We recruited all Death Cases with COVID-19 from Dec 30, 2019 to Feb 16, 2020 in Intensive care unit of Wuhan Jinyintan Hospital.Demographics, basic diseases, X-ray/CT results, possible therapy strategies and test results when their entrance into admission, ICU and 48 h before death were collected and analyzed. Results This study involved 101 COVID-19 dead cases in Intensive care unit of Wuhan Jinyintan Hospital.47 patients went directly to the ICU because of critical condition, and 54 patients were transferred to ICU with aggravated condition.57 (56.44%) were laboratory confirmed by RT-PCR, and 44 (43.6%) were consistent with clinical diagnostic criteria.The cases included 64 males and 37 females with average age of 65.46 years (SD 9.74). The blood type distribution was significantly different, with type A 44.44%, type B 29.29%, type AB 8.08% and type O 18.19%.The clinical manifestations of new coronavirus pneumonia are non-specific,the common symptom was fever (91 [90.10%] of 101 patients),Cough (69[68.32%]) and dyspnea (75[74.26%]). Neutrophils, PCT, CRP,IL-6,D-dimer gradually increased as time went on.Myocardial enzymes were abnormal in most patients at admission,with the progress of the disease, myocardial damage indicators were significantly increased.61(60.40%) used antiviral drugs,59(58.42%) used glucocorticoids, 63.37% used intravenous immunoglobulins, and 44.55% used thymosin preparations. All patients received antibiotic treatment, 63(62.38%) used restricted antibiotics, 23(22.78%) used antifungal drugs.84(83.17%) used non-invasive ventilator or high-flow oxygen therapy equipment, and 76.24% used invasive mechanical ventilation. 7 patients were treated with ECMO and 8 patients were treated with CRRT.The median time from ARDS to invasive mechanical ventilation was 3.00 days(IQR 0.00-6.00). The duration of invasive mechanical ventilation was 5 days (IQR2.00-8.00). Conclusions Critical COVID-19 can cause fatal respiratory distress syndrome and multiple organ failure with high mortality rate. Heart may be the earliest damaged organ except the lungs. Secondary infection in the later period is worthy of attention.


title: Simulations of the spread of COVID-19 and control policies in Tunisia

text: We develop and analyze in this work an epidemiological model for COVID-19 using Tunisian data. Our aims are first to evaluate Tunisian control policies for COVID-19 and secondly to understand the effect of different screening, quarantine and containment strategies and the rule of the asymptomatic patients on the spread of the virus in the Tunisian population. With this work, we show that Tunisian control policies are efficient in screening infected and asymptomatic individuals and that if containment and curfew are maintained the epidemic will be quickly contained.


Addressing therapeutic questions to help Canadian physicians optimize asthma management for their patients during the COVID-19 pandemic


title: Association between NSAIDs use and adverse clinical outcomes among adults hospitalised with COVID-19 in South Korea: A nationwide study

text: BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) may exacerbate COVID-19 and worsen associated outcomes by upregulating the enzyme that SARS-CoV-2 binds to enter cells. However, to our knowledge, no study has examined the association between NSAID use and the risk of COVID-19-related outcomes among hospitalised patients. METHODS: We conducted a population-based cohort study using South Korea nationwide healthcare database, which contains data of all subjects who received a test for COVID-19 (n=69,793) as of April 8, 2020. We identified a cohort of adults hospitalised with COVID-19, where cohort entry was the date of hospitalisation. NSAIDs users were those prescribed NSAIDs while hospitalised and non-users were those not prescribed NSAIDs. Our primary outcome was a composite of death, intensive care unit admission, mechanical ventilation use, and sepsis; secondary outcome was cardiovascular or renal complications. We conducted logistic regression analysis to estimate adjusted odds ratio (aOR) with 95% confidence intervals (CI) for the risk of these outcomes associated with NSAIDs users versus non-users, using propensity score-inverse probability of treatment weighting to minimize potential confounding. In sensitivity analyses, we compared NSAIDs to paracetamol (acetaminophen) to minimize confounding by indication. FINDINGS: Of 1,824 adults hospitalised with COVID-19 (mean age 44.7 years; female 59%), 285 were NSAIDs users and 1,539 were non-users. Compared with non-users, NSAIDs users were associated with increased risks of the primary composite outcome (aOR 1.54, 95% CI 1.11-2.15) and cardiovascular or renal complications (aOR 2.64, 95% CI 1.67-4.16). The association with primary outcome remained consistent when comparing NSAIDs to paracetamol (aOR 1.31, 95% CI 0.89-1.95). INTERPRETATION: Use of NSAIDs, compared with non-use, is associated with worse outcomes among hospitalised COVID-19 patients. While awaiting the results of confirmatory studies, we suggest NSAIDs be used with caution as the harms associated with their use may outweigh their benefits in this population.


title: Preliminary estimating the reproduction number of the coronavirus disease (COVID-19) outbreak in Republic of Korea and Italy by 5 March 2020

text: The novel coronavirus disease 2019 (COVID-19) outbreak and Italy has caused 6088 cases and 41 deaths in Republic of Korea and 3144 cases and 107 death in Italy by 5 March 2020. We modeled the transmission process in Republic of Korea and Italy with a stochastic model and estimated the basic reproduction number R0 as 2.6 (95% CI: 2.3-2.9) or 3.2 (95% CI: 2.9-3.5) in Republic of Korea, under the assumption that the exponential growth starting on 31 January or 5 February 2020, and 2.6 (95% CI: 2.3-2.9) or 3.3 (95% CI: 3.0-3.6) in Italy, under the assumption that the exponential growth starting on 5 February or 10 February 2020. Estimates of dispersion term (k) were 10 (95% CI: 5-56) or 22 (95% CI: 8-61) in Republic of Korea, and 13 (95% CI: 5-61) or 37 (95% CI: 13-61) in Italy, and all of which imply few super-spreading events.


title: Differentiating COVID-19 from other types of pneumonia with convolutional neural networks

text: INTRODUCTION A widely-used method for diagnosing COVID-19 is the nucleic acid test based on real-time reverse transcriptase-polymerase chain reaction (RT-PCR). However, the sensitivity of real time RT-PCR tests is low and it can take up to 8 hours to receive the test results. Radiologic methods can provide higher sensitivity. The aim of this study is to investigate the use of X-ray and convolutional neural networks for the diagnosis of COVID-19 and to differentiate it from viral and/or bacterial pneumonia, as 2-class (bacterial pneumonia vs COVID-19 and viral pneumonia vs COVID-19) and 3-class (bacterial pneumonia, COVID-19, and healthy group (BCH), and among viral pneumonia, COVID-19, and healthy group (VCH)) experiments. METHODS 225 COVID-19, 1,583 healthy control, 2,780 bacterial pneumonia, and 1,493 viral pneumonia chest X-ray images were used. 2-class- and 3-class-experiments were performed with different convolutional neural network (ConvNet) architectures, with different variations of convolutional layers and fully-connected layers. RESULTS The results showed that bacterial pneumonia vs COVID-19 and viral pneumonia vs COVID-19 reached a mean ROC AUC of 97.32% and 96.80%, respectively. In the 3-class-experiments, macro-average F1 scores of 95.79% and 94.59% were obtained in terms of detecting COVID-19 among BCH and VCH, respectively. CONCLUSIONS The ConvNet was able to distinguish the COVID-19 images among non-COVID-19 images, namely bacterial and viral pneumonia as well as normal X-ray images.


Un nuevo coronavirus emerge


title: Alveolar early progenitors in the aged human lung have increased expression of ACE2 accompanied with genes involved in beta-amyloid clearance: Indication of SARS-CoV-2 also using soluble ACE2 in aged-lungs to enter ACE2-negative cells

text: COVID-19 is the current pandemic caused by severe acute respiratory syndrome virus 2 (SARS-CoV-2) that uses ACE2 protein on the cell surface. By analyzing publicly available datasets, I uncovered that alveolar early progenitors (AEP), a subset of the type-2 pneumocytes, showed increased ACE2 expression in the older lungs. AEPs co-express TMPRSS2, CTSL. Aged AEP-gene expression signature suggested an active response to beta-amyloid-induced ACE2 shedding, to limit the intercellular beta-amyloid accumulation in otherwise healthy human lungs. Susceptibility of AEP to SARS-CoV2 and ACE2 secretory capacity of these cells makes aged human lung sensitive for rapid-infection, by a possible in-solution ACE2 binding and entry into ACE2-negative cells, thereby increasing the target cell diversity and numbers. Single-cell analysis of COVID19 patients with moderate and severe infections, clearly showed that severe infections showed SARS-CoV-2 transcript in ACE2-negative TMPRSS-negative but CTSL-positive cell types in their bronchoalveolar lavage fluid, validating in-solution ACE2-binding enabling infection.


title: Modified SEIR and AI prediction of the epidemics trend of COVID-19 in China under public health interventions.

text: Background The coronavirus disease 2019 (COVID-19) outbreak originating in Wuhan, Hubei province, China, coincided with chunyun, the period of mass migration for the annual Spring Festival. To contain its spread, China adopted unprecedented nationwide interventions on January 23 2020. These policies included large-scale quarantine, strict controls on travel and extensive monitoring of suspected cases. However, it is unknown whether these policies have had an impact on the epidemic. We sought to show how these control measures impacted the containment of the epidemic. Methods We integrated population migration data before and after January 23 and most updated COVID-19 epidemiological data into the Susceptible-Exposed-Infectious-Removed (SEIR) model to derive the epidemic curve. We also used an artificial intelligence (AI) approach, trained on the 2003 SARS data, to predict the epidemic. Results We found that the epidemic of China should peak by late February, showing gradual decline by end of April. A five-day delay in implementation would have increased epidemic size in mainland China three-fold. Lifting the Hubei quarantine would lead to a second epidemic peak in Hubei province in mid-March and extend the epidemic to late April, a result corroborated by the machine learning prediction. Conclusions Our dynamic SEIR model was effective in predicting the COVID-19 epidemic peaks and sizes. The implementation of control measures on January 23 2020 was indispensable in reducing the eventual COVID-19 epidemic size.


title: Intervention strategies against COVID-19 and their estimated impact on Swedish healthcare capacity

text: Objectives: During March 2020, the COVID-19 pandemic has rapidly spread globally, and non-pharmaceutical interventions are being used to reduce both the load on the healthcare system as well as overall mortality. Design: Individual-based transmission modelling using Swedish demographic and Geographical Information System data and conservative COVID-19 epidemiological parameters. Setting: Sweden Participants: A model to simulate all 10.09 million Swedish residents. Interventions: 5 different non-pharmaceutical public-health interventions including the mitigation strategy of the Swedish government as of 10 April; isolation of the entire household of confirmed cases; closure of schools and non-essential businesses with or without strict social distancing; and strict social distancing with closure of schools and non-essential businesses. Main outcome measures: Estimated acute care and intensive care hospitalisations, COVID-19 attributable deaths, and infections among healthcare workers from 10 April until 29 June. Findings: Our model for Sweden shows that, under conservative epidemiological parameter estimates, the current Swedish public-health strategy will result in a peak intensive-care load in May that exceeds pre-pandemic capacity by over 40-fold, with a median mortality of 96,000 (95% CI 52,000 to 183,000). The most stringent public-health measures examined are predicted to reduce mortality by approximately three-fold. Intensive-care load at the peak could be reduced by over two-fold with a shorter period at peak pandemic capacity. Conclusions: Our results predict that, under conservative epidemiological parameter estimates, current measures in Sweden will result in at least 40-fold over-subscription of pre-pandemic Swedish intensive care capacity, with 15.8 percent of Swedish healthcare workers unable to work at the pandemic peak. Modifications to ICU admission criteria from international norms would further increase mortality.


title: Predicting Long-term Evolution of COVID-19 by On-going Data using Bayesian Susceptible-Infected-Removed Model

text: In this study, we propose a novel statistical method to predict a long-term epidemic evolution based on a on-going data. We developed a Bayesian framework for the Susceptible-Infected-Removed model (Bayesian SIR), and estimated its underlying parameters based on day-by-day timeseries of the cumulative number of infectious individuals. The new Bayesian framework extends the deterministic SIR model to a probabilistic form, which provides an accurate estimation of the underlying system by a short and noisy data. We applied it to the data reported on the Coronavirus Disease 2019 (COVID-19), and made a month long prediction on its evolution. Our simulated test using past timeseries to predict the current data gives a reasonable reliability of the proposed method. Our analysis of the current data detected and warned a rising trend in the countries in Central Asia, Middle East, and South America, while United States or European countries, which have already experienced large numbers of infected cases, are predicted to slow down in the increase.


title: Cholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking membrane fusion

text: Cholesterol 25-hydroxylase (CH25H) is an interferon-stimulated gene (ISG) that shows broad antiviral activities against a wide range of enveloped viruses. Here, using an ISG screen against VSV-SARS-CoV and VSV-SARS-CoV-2 chimeric viruses, we identified CH25H and its enzymatic product 25-hydroxycholesterol (25HC) as potent inhibitors of virus replication. Mechanistically, internalized 25HC accumulates in the late endosomes and blocks cholesterol export, thereby restricting SARS-CoV-2 spike protein catalyzed membrane fusion. Our results highlight a unique antiviral mechanism of 25HC and provide the molecular basis for its possible therapeutic development.


title: Covid-19 Detection using CNN Transfer Learning from X-ray Images

text: The Covid-19 first occurs in Wuhan, China in December 2019. After that the virus spread all around the world and at the time of writing this paper the total number of confirmed cases are above 4 million with over 297000 deaths. Machine learning algorithms built on radiography images can be used as a decision support mechanism to aid radiologists to speed up the diagnostic process. The aim of this work is twofold. First, a quantitative analysis where we evaluate 12 off-the-shelf convolutional neural networks (CNNs) and proposed a simple CNN architecture with less parameters and computational power that can perform as good as Xception and DenseNet architectures if trained on small dataset of chest X-ray images. Secondly, a qualitative investigation to inspect the decisions made by CNNs using a technique known as class activation maps (CAM). Using CAMs, one can map the activations contributed most to the decision of CNNs back to the original image to visualize the most discriminating regions in the input image. Chest X-ray images used in this work are coming from multiple sources which comprises of 154 confirmed COVID-19 images and over 5000 X-rays of normal, bacterial and other viral (non-COVID-19) infections. We conclude that CNN decisions should not be taken into consideration until radiologist/clinicians can visually inspect the region(s) of the input image used by CNNs that lead to its prediction. This work also reports the necessity of segmenting the region of interest (ROI) to prevent CNNs building their decision from features outside ROI.


title: Boosting innate immunity: Asaia bacteria expressing a protein from Wolbachia determine macrophage activation and killing of Leishmania

text: Leishmaniases are severe vector-borne diseases affecting humans and animals, caused by Leishmania protozoans. Immune polarization plays a major role in determining the outcome of Leishmania infections: hosts displaying M1-polarized macrophages are protected, while those biased on the M2 side acquire a chronic infection, that could develop into an overt and potentially deadly disease. The identification of the factors involved in M1 polarization is essential for the design of therapeutic and prophylactic interventions, including vaccines. Infection by the filarial nematode Dirofilaria immitis could be one of the factors that interfere with leishmaniasis in dogs. Indeed, filarial nematodes induce a partial skew of the immune response towards M1, likely caused by their bacterial endosymbionts, Wolbachia. Here we have examined the potential of AsaiaWSP, a bacterium engineered for the expression of the Wolbachia surface protein (WSP), as an inductor of M1 macrophage activation and Leishmania killing. Macrophages stimulated with AsaiaWSP displayed a strong leishmanicidal activity, comparable to that determined by the choice-drug amphotericin B. Additionally, AsaiaWSP determined the expression of markers of classical macrophage activation, including M1 cytokines, ROS and NO, and an increase in phagocytosis activity. Asaia not expressing WSP also induced macrophage activation, although at a lower extent compared to AsaiaWSP. In summary, our study, while providing a strong evidence for the immune-stimulating properties of Wolbachia, highlights the translational potential of AsaiaWSP in the areas of the immune-prophylaxis and therapy of leishmaniases, as well as of other diseases that could be subverted by M1 macrophage activation.


Plastic Surgery Education during the COVID-19 Outbreak: Leveling the Playing Field


docid: gcwecehu

title: Insight towards the effect of the multibasic cleavage site of SARS-CoV-2 spike protein on cellular proteases

text: Severe respiratory syndrome coronavirus 2 (SARS-CoV-2) infection presents an immense global health problem. Spike (S) protein of coronavirus is the primary determinant of its entry into the host as it consists of both receptor binding and fusion domain. While tissue tropism, host range, and pathogenesis of coronavirus are primarily controlled by the interaction of S protein with the cell receptor, it is possible that proteolytic activation of S protein by host cell proteases also plays a decisive role. The host-cell proteases have shown to be involved in the proteolysis of S protein and cleaving it into two functional subunits, S1 and S2, during the maturation process. In the present study, the interaction of S protein of SARS-CoV-2 with different host proteases like furin, cathepsin B, and plasmin has been analyzed. Incorporation of the furin cleavage site (R-R-A-R) in the S protein in SARS-CoV-2 has been studied by mutating the individual amino acid. Our results suggest the polytropic nature of the S protein of SARS-CoV-2. Our analysis indicated that a single amino acid substitution in the polybasic cleavage site of S protein perturb the binding of cellular proteases. This mutation study might help to generate an attenuated SARS-CoV-2. Besides, targeting of host proteases by inhibitors may result in a practical approach to stop the cellular spread of SARS-CoV-2 and to develop its antiviral.


title: Comparative Survival Analysis of Immunomodulatory Therapy for COVID-19 'Cytokine Storm': A Retrospective Observational Cohort Study

text: Background: Cytokine storm is a marker of COVID-19 illness severity and increased mortality. Immunomodulatory treatments have been repurposed to improve mortality outcomes. Methods: We conducted a retrospective analysis of electronic health records across the Northwell Health system. COVID-19 patients hospitalized between March 1, 2020 and April 15, 2020, were included. Cytokine storm was defined by inflammatory markers: ferritin >700ng/mL, C-reactive protein >30mg/dL, or lactate dehydrogenase >300U/L. Patients were subdivided into six groups -no immunomodulatory treatment (standard of care) and five groups that received either corticosteroids, anti-interleukin 6 (IL-6) antibody (tocilizumab) or anti-IL-1 therapy (anakinra) alone or in combination with corticosteroids. The primary outcome was hospital mortality. Results: There were 3,098 patients who met inclusion criteria. The most common comorbidities were hypertension (40-56%), diabetes (32-43%) and cardiovascular disease (2-15%). Patients most frequently met criteria with high lactate dehydrogenase (74.8%) alone, or in combination, followed by ferritin (71.4%) and C-reactive protein (9.4%). More than 80% of patients had an elevated D-dimer. Patients treated with a combination of tocilizumab and corticosteroids (Hazard Ratio [HR]: 0.459, 95% Confidence Interval [CI]: 0.295-0.714; p<0.0001) or corticosteroids alone (HR: 0.696, 95% CI: 0.512-0.946; p=0.01) had improved hospital survival compared to standard of care. Corticosteroids and tocilizumab was associated with increased survival when compared to corticosteroids and anakinra (HR: 0.612, 95% CI: 0.391-0.958; p-value=0.02). Conclusions: When compared to standard of care, corticosteroid and tocilizumab used in combination, or corticosteroids alone, was associated with reduced hospital mortality for patients with COVID-19 cytokine storm.


title: Mutations can reveal how the coronavirus moves—but they’re easy to overinterpret

text: Immediately after Christian Drosten published a genetic sequence of the novel coronavirus online on 28 February, he took to Twitter to issue a warning As the virus has raced around the world, more than 350 genome sequences have been shared on the online platform GISAID They hold clues to how the new virus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading and evolving But because the sequences represent a tiny fraction of cases and show few telltale differences, they are easy to overinterpret, as Drosten realized A virologist at the Charité University Hospital in Berlin, he had sequenced the virus from a German patient infected with COVID-19 in Italy The genome looked similar to that of a virus found in a patient in Munich, the capital of Bavaria, more than 1 month earlier;both shared three mutations not seen in early sequences from China Drosten realized this could give rise to the idea that the Italian outbreak was “seeded” by the one in Bavaria, which state public health officials said had been quashed by tracing and quarantining all contacts of the 14 confirmed cases But he thought it was just as likely that a Chinese variant carrying the three mutations had taken independent routes to both countries The newly sequenced genome “is not sufficient to claim a link between Munich and Italy,” Drosten tweeted


title: BioLaboro: A bioinformatics system for detecting molecular assay signature erosion and designing new assays in response to emerging and reemerging pathogens

text: Background Emerging and reemerging infectious diseases such as the novel Coronavirus disease, COVID-19 and Ebola pose a significant threat to global society and test the public health community’s preparedness to rapidly respond to an outbreak with effective diagnostics and therapeutics. Recent advances in next generation sequencing technologies enable rapid generation of pathogen genome sequence data, within 24 hours of obtaining a sample in some instances. With these data, one can quickly evaluate the effectiveness of existing diagnostics and therapeutics using in silico approaches. The propensity of some viruses to rapidly accumulate mutations can lead to the failure of molecular detection assays creating the need for redesigned or newly designed assays. Results Here we describe a bioinformatics system named BioLaboro to identify signature regions in a given pathogen genome, design PCR assays targeting those regions, and then test the PCR assays in silico to determine their sensitivity and specificity. We demonstrate BioLaboro with two use cases: Bombali Ebolavirus (BOMV) and the novel Coronavirus 2019 (SARS-CoV-2). For the BOMV, we analyzed 30 currently available real-time reverse transcription-PCR assays against the three available complete genome sequences of BOMV. Only two met our in silico criteria for successful detection and neither had perfect matches to the primer/probe sequences. We designed five new primer sets against BOMV signatures and all had true positive hits to the three BOMV genomes and no false positive hits to any other sequence. Four assays are closely clustered in the nucleoprotein gene and one is located in the glycoprotein gene. Similarly, for the SARS-CoV-2, we designed five highly specific primer sets that hit all 145 whole genomes (available as of February 28, 2020) and none of the near neighbors. Conclusions Here we applied BioLaboro in two real-world use cases to demonstrate its capability; 1) to identify signature regions, 2) to assess the efficacy of existing PCR assays to detect pathogens as they evolve over time, and 3) to design new assays with perfect in silico detection accuracy, all within hours, for further development and deployment. BioLaboro is designed with a user-friendly graphical user interface for biologists with limited bioinformatics experience.


title: Rethinking antiviral effects for COVID-19 in clinical studies: early initiation is key to successful treatment

text: Development of an effective antiviral drug for COVID-19 is a global health priority. Although several candidate drugs have been identified through in vitro and in vivo models, consistent and compelling evidence for effective drugs from clinical studies is limited. The lack of evidence could be in part due to heterogeneity of virus dynamics among patients and late initiation of treatment. We first quantified the heterogeneity of viral dynamics which could be a confounder in compassionate use programs. Second, we demonstrated that an antiviral drug is unlikely to be effective if initiated after a short period following symptom onset. For accurate evaluation of the efficacy of an antiviral drug for COVID-19, antiviral treatment should be initiated before or soon after symptom onset in randomized clinical trials.


Radiological follow-up of twelve COVID-19 patients with initially normal chest CT.


title: Pandemic and lockdown: a territorial approach to COVID-19 in China, Italy and the United States

text: Three months into the Covid-19 crisis, lockdown has become a global response to the pandemic. Why have so many countries resorted to lockdown? How is it being implemented in different places? Why have some places had more success with lockdowns and others not? What does the effectiveness of lockdowns tell us about the local institutions entrusted with enforcing them? This paper compares how lockdown orders have been implemented in China, Italy, and the U.S. The analysis points to two major factors that have shaped the enforcement: tensions between national and local governments, and the strength of local territorial institutions.


Cancelled elderly exercise sessions during the COVID-19 crisis: can physical therapists help from their homes?


title: Perspectives on repositioning chloroquine and hydroxychloroquine for the treatment of Covid-19

text: Coronavirus disease 2019 (COVID-19) is now spreading as a pandemic ravaging the whole world In the absence of a vaccine and an effective antiviral chemotherapy, there is currently an intense global interest in repositioning chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) to combat the pandemic CQ has been used for decades for the treatment and prophylaxis against malaria in endemic countries It is readily available and has also been manufactured in these countries CQ is cheap, stable under field conditions and has been well tolerated as an antimalarial This experience could be adapted to deploy CQ or HCQ for prophylaxis or treatment of COVID19 if strong evidence could be generated for these uses We believe that well-designed drug trials should be initiated in malaria-endemic countries, taking into account the local context of the epidemic and the capacity of the health system in combating it In this paper, we are presenting the current status of evidence for using CQ and HCQ against COVID19


title: Modelling-based evaluation of the effect of quarantine control by the Chinese government in the coronavirus disease 2019 outbreak

text: The novel coronavirus disease 2019 (COVID-19) epidemic, which was first identified in Wuhan, China in December 2019, has rapidly spread all over China and across the world. By the end of February 2020, the epidemic outside Hubei province in China has been well controlled, yet the next wave of transmission in other countries may have just begun. A retrospective modeling of the transmission dynamics would provide insights into the epidemiological characteristics of the disease and evaluation of the effectiveness of the strict measures that have been taken by central and local governments of China. Using a refined susceptible-exposed-infectious-removed (SEIR) transmission model and a new strategy of model fitting, we were able to estimate model parameters in a dynamic manner. The resulting parameter estimation can well reflect the prevention policy scenarios. Our simulation results with different degrees of government control suggest that the strictly enforced quarantine and travel ban have significantly decreased the otherwise uncontrollable spread of the disease. Our results suggest similar measures should be considered by other countries that are of high risk of COVID-19 outbreak.


Surgical specialties launch national COVID-19 tracheostomy service evaluation


title: Myocardial characteristics as the prognosis for COVID-19 patients

text: Background Amid the crisis of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), front-line clinicians in collaboration with backstage medical researchers analyzed clinical characteristics of COVID-19 patients and reported the prognosis using myocardial data records upon hospitalization. Methods We reported 135 cases of laboratory-confirmed COVID-19 patients admitted in The First People's Hospital of Jiangxia District in Wuhan, China. Demographic data, medical history, and laboratory parameters were taken from inpatient records and compared between patients at the Intensive Care Unit (ICU) and non-ICU isolation wards for prognosis on disease severity. In particular, survivors and non-survivors upon ICU admission were compared for prognosis on disease mortality. Results For COVID-19 patients, blood test results showed more significantly deranged values in the ICU group than those in non-ICU. Among those parameters for ICU patients, myocardial variables including troponin T, creatine kinase isoenzymes, myoglobin, were found significantly higher in non-survivors than in survivors. Conclusions Upon hospitalization abnormal myocardial metabolism in COVID-19 patients could be prognostic indicators of a worsened outcome for disease severity and mortality.


title: Application of pooled testing in screening and estimating the prevalence of Covid-19

text: The recent emergence of the COVID-19 pandemic has posed an unprecedented healthcare challenge and catastrophic economic and social consequences to the countries across the world. The situation is even worse for emerging economies like India. WHO recommends mass scale testing as one of the most effective ways to contain its spread and fight the pandemic. But, due to the high cost and shortage of test kits, specifically in India, the testing is restricted to only those who are symptomatic. In this context, pooled testing is recommended by some experts as a partial solution to overcome this problem. In this article, we explain the basic statistical theory behind the pooled testing procedure for screening as well as prevalence estimation. In real world situations, the tests are imperfect, and lead to false positive and false negative results. We provide theoretical explanation of the impact of these diagnostic errors on the performances of individual testing and pooled testing procedures. Finally, we study the effect of misspecification of sensitivity and specificity of tests on the estimate of prevalence, an issue, which is debated a lot among the scientists in the context of COVID-19. Our theoretical investigations lead to some interesting and precise understanding of some of these issues.


title: Development and utilization of an intelligent application for aiding COVID-19 diagnosis

text: On basis of laboratory examinations indicators from a total of 620 samples, a machine learning-based diagnosis model was developed, and subsequently implemented as a COVID-19 diagnosis aid APP. External validation showed satisfiable model prediction performance (i.e., AUC= 0.872) which guarantees the promising use of this tool for extensive screening.


title: Indications for healthcare surge capacity in European countries facing an exponential increase in COVID19 cases

text: European healthcare systems face extreme pressure from COVID-19. We estimate such pressure by relating both country-specific accumulated COVID-19 deaths (intensity-approach) and active COVID-19 cases (magnitude-approach) to measures of healthcare system capacity: hospital beds, healthcare workers and healthcare expenditure. On March 25, 2020 - relative to Italy on March 11- we found Spain, The Netherlands and France to experience the highest pressure using the intensity-approach with a composite measure for healthcare capacity. For updates see www.covid-hcpressure.org


title: Mathematical model describing CoViD-19 in Sao Paulo State, Brazil - Evaluating isolation as control mechanism and forecasting epidemiological scenarios of release

text: We formulated a mathematical model considering young (below 60 years old) and elder (above 60 years) subpopulations to describe the introduction and dissemination of new coronavirus epidemics in the Sao Paulo State, Brazil. From the data collected in Sao Paulo State, we estimated the model parameters and calculated the basic reproduction number as R0 = 6.828. Considering isolation as a control mechanism, we varied the releasing proportions of young and elder persons to assess their epidemiological impacts. The best scenarios were release of young persons, but maintaining elder persons isolated. To avoid the collapse of the health care system, the isolation must be at least 80%.


docid: xidoktjb

title: COVID-19 in Singapore and Malaysia: Rising to the challenges of orthopaedic practice in an evolving pandemic

text: With the increasing number of COVID-19 cases and related deaths worldwide, we decided to share the development of this condition in Singapore and Malaysia. First few cases were diagnosed in the two countries at the end of January 2020, and the numbers have surged to thousands by end of March 2020. We will focus on strategies adopted by the government and also the Orthopaedic community of the two countries up till the beginning of April 2020. We hope that by sharing of relevant information and knowledge on how we are managing the COVID-19 condition, we can help other communities, and health care workers to more effectively overcome this pandemic.


title: Disproportionate incidence of COVID-19 in African Americans correlates with dynamic segregation

text: Socio-economic disparities quite often have a central role in the unfolding of large-scale catastrophic events. One of the most concerning aspects of the ongoing COVID-19 pandemics is that it disproportionately affects people from Black and African American backgrounds creating an unexpected infection gap. Interestingly, the abnormal impact on these ethnic groups seem to be almost uncorrelated with other risk factors, including co-morbidity, poverty, level of education, access to healthcare, residential segregation, and response to cures. A proposed explanation for the observed incidence gap is that people from African American backgrounds are more often employed in low-income service jobs, and are thus more exposed to infection through face-to-face contacts, but the lack of direct data has not allowed to draw strong conclusions in this sense so far. Here we introduce the concept of dynamic segregation, that is the extent to which a given group of people is internally clustered or exposed to other groups, as a result of mobility and commuting habits. By analysing census and mobility data on more than 120 major US cities, we found that the dynamic segregation of African American communities is significantly associated with the weekly excess COVID-19 incidence and mortality in those communities. The results confirm that knowing where people commute to, rather than where they live, is much more relevant for disease modelling.


title: Estimated Sp02/Fio2 ratio to predict mortality in patients with suspected COVID-19 in the Emergency Department: a prospective cohort study

text: Background This study examined whether the presence and severity of Type 1 Respiratory Failure (T1RF), as measured by the ratio of pulse oximetry to estimated fraction of inspired oxygen (SpO2/eFiO2 ratio), is a predictor of in-hospital mortality in patients presenting to the ED with suspected COVID19 infection. Methods We undertook a prospective observational cohort study of patients admitted to hospital with suspected COVID-19 in a single ED in England. We used univariate and multiple logistic regression to examine whether the presence and severity of T1RF in the ED was independently associated with in-hospital mortality. Results 180 patients with suspected COVID19 infection met the inclusion criteria for this study, of which 39 (22%) died. Severity of T1RF was associated with increased mortality with odds ratios (OR) and 95% confidence intervals of 1.58 (0.49 to 5.14), 3.60 (1.23 to 10.6) and 18.5 (5.65 to 60.8) for mild, moderate and severe T1RF, respectively. After adjusting for age, gender, pre-existing cardiovascular disease, neutrophil-lymphocyte ration (NLR) and estimated glomerular filtration rate (eGFR), the association remained, with ORs of 0.63 (0.13 to 3.03), 3.95 (0.94 to 16.6) and 45.8 (7.25 to 290). The results were consistent across a number of sensitivity analyses. Conclusions Severity of T1RF in the ED is an important prognostic factor of mortality in patients admitted with suspected COVID19 infection. Current prediction models frequently do not include this factor and should be applied with caution. Further large scale research on predictors of mortality in COVID19 infection should include SpO2/eFiO2 ratios or a similar measure of respiratory dysfunction.


docid: roiquyvz

title: Clinical features of coronavirus disease 2019 (COVID-19) in a cohort of patients with disability due to spinal cord injury

text: Study design: Cohort study of patients with spinal cord injury (SCI) Objectives: To describe the clinical and analytical features of a Covid-19 infected cohort with SCI to contribute new knowledge for a more accurate diagnosis and to outline prevention measures. Setting: This study was conducted at the National Hospital for Paraplegics (Toledo, Spain). Methods: A cohort analysis of seven patients with SCI infected by Covid-19 was carried out. Diagnosis was confirmed with reverse transcriptase polymerase chain reaction (RT-PCR) of nasal exudate or sputum samples. Clinical, analytical and radiographic findings were registered. Results: RT-PCR detected COVID-19 infection in all patients, affecting males and people with a cervical level of injury more often (5 out 7). The average delay for diagnostic confirmation was 4 days (interquartile range, 1-10). Fever was the most frequent symptom (6 out of 7). The second most common symptom was asthenia (4 out of 7), followed by dyspnea, cough and expectoration (3 out of 7 for each symptom). The MEWS score for Covid-19 severity rating was classified as severe in 5 out of 7. All but one patient showed radiological alterations evident in chest X-Rays at the time of diagnosis. All patients recovered gradually. Conclusion: Our patients with SCI and Covid-19 infection exhibited fewer symptoms than the general population. Furthermore, they presented similar or greater clinical severity. The clinical evolution was not as pronounced as had been expected. This study recommends close supervision of the SCI population to detect early compatible signs and symptoms of Covid-19 infection.


History of Infectious Disease Pandemics in Urban Societies


title: E-learning in the teaching of mathematics: An educational experience in adult high school

text: Currently, the e-learning method, due to the period of confinement that is occurring due to COVID-19, has increased its use and application in the teaching and learning processes. The main objective of this research is to identify the effectiveness of the e-learning method in the teaching of mathematics with adults who are in high school, in contrast to the traditional expository method. The study developed is quantitative, descriptive and correlational. The research design is quasi-experimental, with a control group and an experimental group. The results show that the use of the e-learning method has a positive influence on motivation, autonomy, participation, mathematical concepts, results and grades. It can be concluded that the e-learning method leads to improvement in adult students who are studying the mathematical subject in the educational stage of high school, provided that it is compared with the expository method. Therefore, this method is considered effective for its implementation in adults.


title: SARS-CoV-2 Seroprevalence Rates of Children in Louisiana During the State Stay at Home Order.

text: Children (less than 19 years) account for 20% of the US population but currently represent less than 2% of coronavirus disease 2019 (COVID-19) cases. Because infected children often have few or no symptoms and may not be tested, the extent of infection in children is poorly understood. METHODS During the March 18th-May 15th 2020 Louisiana Stay At Home Order, 1690 blood samples from 812 individuals from a Childrens Hospital were tested for antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Demographics, COVID-19 testing, and clinical presentation abstracted from medical records were compared with local COVID-19 cases. RESULTS In total, 62 subjects (7.6%) were found to be seropositive. The median age was 11 years with 50.4% female. The presenting complaint of seropositive patients was chronic illness (43.5%). Only 18.2% had a previous positive COVID-19 PCR or antibody test. Seropositivity was significantly associated with parish (counties), race, and residence in a low-income area. Importantly, seropositivity was linearly correlated with cumulative COVID-19 case number for all ages by parish. CONCLUSION In a large retrospective study, the seropositivity prevalence for SARS-CoV-2 in children in Louisiana during the mandated Stay At Home Order was 7.6%. Residence location, race, and lower socioeconomic factors were linked to more frequent seropositivity in children and correlated to regional COVID-19 case rates. Thus, a significant number of children in Louisiana had SARS-CoV-2 infections that went undetected and unreported and may have contributed to virus transmission.


title: The enzymatic activity of the nsp14 exoribonuclease is critical for replication of Middle East respiratory syndrome-coronavirus

text: Coronaviruses (CoVs) stand out for their large RNA genome and complex RNA-synthesizing machinery comprising 16 nonstructural proteins (nsps). The bifunctional nsp14 contains an N-terminal 3’-to-5’ exoribonuclease (ExoN) and a C-terminal N7-methyltransferase (N7-MTase) domain. While the latter presumably operates during viral mRNA capping, ExoN is thought to mediate proofreading during genome replication. In line with such a role, ExoN-knockout mutants of mouse hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus (SARS-CoV) were previously found to have a crippled but viable hypermutation phenotype. Remarkably, using an identical reverse genetics approach, an extensive mutagenesis study revealed the corresponding ExoN-knockout mutants of another betacoronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), to be non-viable. This is in agreement with observations previously made for alpha- and gammacoronaviruses. Only a single MERS-CoV ExoN active site mutant could be recovered, likely because the introduced D191E substitution is highly conservative in nature. For 11 other MERS-CoV ExoN active site mutants, not a trace of RNA synthesis could be detected, unless – in some cases – reversion had first occurred. Subsequently, we expressed and purified recombinant MERS-CoV nsp14 and established in vitro assays for both its ExoN and N7-MTase activities. All ExoN knockout mutations that were lethal when tested via reverse genetics were found to severely decrease ExoN activity, while not affecting N7-MTase activity. Our study thus reveals an additional function for MERS-CoV nsp14 ExoN, which apparently is critical for primary viral RNA synthesis, thus differentiating it from the proofreading activity thought to boost long-term replication fidelity in MHV and SARS-CoV. Importance The bifunctional nsp14 subunit of the coronavirus replicase contains 3’-to-5’ exoribonuclease (ExoN) and N7-methyltransferase (N7-MTase) domains. For the betacoronaviruses MHV and SARS-CoV, the ExoN domain was reported to promote the fidelity of genome replication, presumably by mediating some form of proofreading. For these viruses, ExoN knockout mutants are alive while displaying an increased mutation frequency. Strikingly, we now established that the equivalent knockout mutants of MERS-CoV ExoN are non-viable and completely deficient in RNA synthesis, thus revealing an additional and more critical function of ExoN in coronavirus replication. Both enzymatic activities of (recombinant) MERS-CoV nsp14 were evaluated using newly developed in vitro assays that can be used to characterize these key replicative enzymes in more detail and explore their potential as target for antiviral drug development.


title: Importance of suppression and mitigation measures in managing COVID-19 outbreaks

text: I employ a simple mathematical model of an epidemic process to evaluate how three basic quantities: the reproduction number (R), the number of infectious individuals (I), and total community size (N) affect strategies to control COVID-19. Numerical simulations show that strict suppression measures at the beginning of an epidemic can create low infectious numbers, which thereafter can be managed by mitigation measures over longer periods to flatten the epidemic curve. The stronger the suppression measure, the faster it achieves the low numbers of infections that are conducive to subsequent management. Our results on short-term strategies point to either a two-step control strategy, following failed mitigation, that begins with suppression of the reproduction number, Rc, below 1.0, followed by renewed mitigation measures that manage the epidemic by maintaining Rc at approximately 1.0, or should suppression not be feasible, a progressive lowering of Rc below 1.0. The full sequence of measures that we are observing in a number of countries, and likely to see in the longer term, can be symbolically represented as: R0 → Rc<R0 → Rc<<1.0 → Rc≈1.0 → Rc<1.0. We discuss the predictions of this analysis and how it fits into longer-term sequences of measures.


title: Rapid inactivation of SARS-CoV-2 with Deep-UV LED irradiation

text: The spread of novel coronavirus disease 2019 (COVID-19) infections worldwide has raised concerns about the prevention and control of SARS-CoV-2. Devices that rapidly inactivate viruses can reduce the chance of infection through aerosols and contact transmission. This in vitro study demonstrated that irradiation with a deep ultraviolet light-emitting diode (DUV-LED) of 280 ±5 nm wavelength rapidly inactivates SARS-CoV-2 obtained from a COVID-19 patient. Development of devices equipped with DUV-LED is expected to prevent virus invasion through the air and after touching contaminated objects.


title: Expert consensus on clinical management strategy for patients with thoracic trauma during the epidemic period of COVID-19/ 新 型 冠 状 病 毒 肺 炎 疫 情 期 间 胸 外 伤 患 者 临 床 管 理 策 略 专 家共识

text: Since December 2019, a corona virus disease 2019 (COVID-19) has been continuing to spread throughout China. This epidemic is characterized by strong infectivity and concealment. China's domestic epidemic is gradually under control by strict quarantine and control measures, meanwhile the incidence of trauma has reduced. However, with the resumption of industry and traffic, the chest trauma caused mainly by traffic accidents and high falling has increased gradually, great risks and challenges are faced in clinical treatment. Therefore, combined with the current epidemic environment and the treatment characteristics of thoracic trauma, experts from the Thoracic Trauma Group, Thoracic Surgery Branch of China International Exchange and Promotion Association for Medical and Health Care and Chest Trauma Management Committee, Guangdong Association of Thoracic Disease develop an "Expert consensus on clinical management strategy for patients with thoracic trauma during the epidemic period of COVID-19 pneumonia". In order to promote the treatment of chest trauma in a scientific and orderly way, the consensus elaborated 4 parts, including classification and treatment strategy for patients with thoracic trauma required a surgical procedure, non-operative treatment of patients with thoracic trauma, management process of chest trauma, and protection and management of ward.


title: Alternative metrics for assessing the social impact of tourism research

text: Alternative metrics are increasingly used to measure the social impact of research. This article seeks to analyze the social impact of research in the field of tourism. For this purpose, we will determine the extent to which the articles in this field reach society by examining the scores they achieve on social media and studying the correlation between scientific impact and social impact. Altmetric information will be used for data extraction and analysis. The results show a low correlation between citations and the Altmetric Attention Score (AAS), as well as a presence that is not captured by most publications in the field of study. Interestingly, publications with higher AASs are concentrated in the same journals. The article concludes by determining that alternative metrics can be used to complement academic impact but cannot be a substitute for it. Further progress is needed in the development of a framework that unifies both impacts.


title: The incubation period of 2019-nCoV infections among travellers from Wuhan, China

text: Currently, a novel coronavirus 2019-nCoV causes an outbreak of viral pneumonia in Wuhan, China. Little is known about its epidemiological characteristics. Using the travel history and symptom onset of 88 confirmed cases that were detected outside Wuhan, we estimate the mean incubation period to be 6.4 (5.6 - 7.7, 95% CI) days, ranging from 2.1 to 11.1 days (2.5th to 97.5th percentile). These values help to inform case definitions for 2019-nCoV and appropriate durations for quarantine.


title: SARS-CoV-2 infects and induces cytotoxic effects in human cardiomyocytes

text: Background The coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has emerged as global pandemic. SARS-CoV-2 infection can lead to elevated markers of cardiac injury associated with higher risk of mortality in COVID-19 patients. It is unclear whether cardiac injury may have been caused by direct infection of cardiomyocytes or is mainly secondary to lung injury and inflammation. Here we investigate whether human cardiomyocytes are permissive for SARS-CoV-2 infection. Methods Infection was induced by two strains of SARS-CoV-2 (FFM1 and FFM2) in human induced pluripotent stem cells-derived cardiomyocytes (hiPS-CM) and in two models of human cardiac tissue. Results We show that SARS-CoV-2 infects hiPS-CM as demonstrated by detection of intracellular double strand viral RNA and viral spike glycoprotein protein expression. Increasing concentrations of virus RNA are detected in supernatants of infected cardiomyocytes, which induced infections in CaCo-2 cell lines documenting productive infections. SARS-COV-2 infection induced cytotoxic and pro-apoptotic effects and abolished cardiomyocyte beating. RNA sequencing confirmed a transcriptional response to viral infection as demonstrated by the up-regulation of genes associated with pathways related to viral response and interferon signaling, apoptosis and reactive oxygen stress. SARS-CoV-2 infection and cardiotoxicity was confirmed in a iPS-derived human 3D cardiosphere tissue models. Importantly, viral spike protein and viral particles were detected in living human heart slices after infection with SARS-CoV-2. Conclusions The demonstration that cardiomyocytes are permissive for SARS-CoV-2 infection in vitro warrants the further in depth monitoring of cardiotoxic effects in COVID-19 patients. Clinical Perspective What is New? This study demonstrates that human cardiac myocytes are permissive for SARS-CoV-2 infection. The study documents that SARS-CoV-2 undergoes a full replicatory circle and induces a cytotoxic response in cardiomyocytes. Infection was confirmed in two cardiac tissue models, including living human heart slices. What are the Clinical Implications? The study may provide a rational to explain part of the cardiotoxicity observed in COVID-19 patients The demonstration of direct cardiotoxicity induced by SARS-CoV-2 warrants an in depth further analysis of cardiac tissue of COVID-19 patients and a close monitoring for putative direct cardiomyocyte injury. The established models can be used to test novel therapeutic approaches targeting COVID-19.


docid: njmoboac

title: Preparation for Possible Sustained Transmission of 2019 Novel Coronavirus: Lessons From Previous Epidemics.