title: Massive Multiplexing Can Deliver a $1 Test for COVID-19

text: The severe acute respiratory syndrome virus, SARS-CoV-2 (hereafter COVID-19), rapidly achieved global pandemic status, provoking large-scale screening programs in many nations. Their activation makes it imperative to identify methods that can deliver a diagnostic result at low cost. This paper describes an approach which employs sequence variation in the gene coding for its envelope protein as the basis for a scalable, inexpensive test for COVID-19. It achieves this by coupling a simple RNA extraction protocol with low-volume RT-PCR, followed by E-Gel screening and sequencing on high-throughput platforms to analyze 10,000 samples in a run. Slight modifications to the protocol could support screening programs for other known viruses and for viral discovery. Just as the $1,000 genome is transforming medicine, a $1 diagnostic test for viral and bacterial pathogens would represent a major advance for public health.


title: The Computational Patient has Diabetes and a COVID

text: Medicine is moving from reacting to a disease to prepare personalised and precision paths to well being. The complex and multi level pathophysiological patterns of most diseases require a systemic medicine approach and are challenging current medical therapies. Computational medicine is a vibrant interdisciplinary field that could help moving from an organ-centered to a process-oriented or systemic medicine data analysis. The resulting Computational patient may require an international interdisciplinary effort, probably of larger scientific and technological interdisciplinarity than the human genome sequencing. When deployed, it will have a profound impact on how healthcare is delivered to patients. Here we present a Computational patient model that integrates, refine and extend recent specific mechanistic or phenomenological models of cardiovascular, RAS and diabetic processes. Our aim is twofold: analyse the modularity and composability of the models-building blocks of the Computational patient and to study the dynamical properties of well-being and disease states in a broader functional context. We present results from a number of experiments among which we characterise the dynamical impact of covid-19 and T2D diabetes on cardiovascular and inflammation conditions. We tested these experiments under exercise and meals and drug regimen. We report results showing the striking importance of transient dynamical responses to acute state conditions and we provide guidelines for system design principle of the inter-relationship between modules and components for systemic medicine. Finally this initial Computational Patient can be used as a toolbox for further modifications and extensions.


title: Association of Bacille Calmette-Guerin (BCG), Adult Pneumococcal and Adult Seasonal Influenza Vaccines with Covid-19 Adjusted Mortality Rates in Level 4 European countries

text: Introduction Non-specific effects of vaccines have gained increasing interest during the Covid-19 pandemic. In particular, population use of BCG vaccine has been associated with improved outcomes. This study sought to determine the association of population use of BCG, adult pneumococcal and adult seasonal influenza vaccination with Covid-19 mortality when adjusted for a number of confounding variables. Methods: Using publicly available data, mortality adjusted for the timeframe of crisis, population size and population characteristics was calculated. The primary analysis was the relationship between each of the day 15 and day 30 standardised mortality rates and BCG, adult pneumococcal and influenza vaccination scores using unadjusted measures and with adjustment for population structure and case fatality rates. Secondary analyses were measures of case increases and mortality increases from day 15 to day 30 for each of the relative vaccination scores. Finally, we also analysed the peak Z score reflecting increases in total mortality from historical averages reported by EuroMOMO (Euromomo.eu), Results: Following adjustment for the effects of population size, median age, population density, the proportion of population living in an urban setting, life-expectancy, the elderly dependency ratio (or proportion over 65 years), net migration, days from day 1 to lockdown and case-fatality rate, only BCG vaccination score remained significantly associated with Covid-19 mortality at day 30. In the best fit model, BCG vaccination score was associated with a 64% reduction in log(10) mortality per 10 million population (OR 0.362 reduction [95% CI 0.188 to 0.698]), following adjustment for population size, median age, density, urbanization, elderly dependency ratio, days to lockdown, yearly migration and case fatality rate. Conclusion BCG vaccine was associated with reduced mortality rates in level 4 countries while adult pneumococcal and adult seasonal influenza vaccines were not when adjusted for a number of confounding variables. A number of trials are ongoing to determine if BCG is protective against severe Covid-19 infection.


Preventive Measures, Advice, and Vaccinations for Traveling US Veterans


title: Who maintains a good mental health in a locked-down country? A French nationwide online survey of 11,391 participants

text: Background: Lockdown measures induce massive societal perturbations and can differentially affect mental wellbeing in populations depending on individual determinants. We aim at investigating the sociodemographic and environmental determinants of wellbeing during global lockdown due to the SARS-CoV-2 pandemic. Methods: A nationwide survey was sent online to the French population during the second week of global lockdown during the SARS-CoV-2 pandemic, between March 25, 2020 and March 30, 2020. Volunteers were recruited on social networks, online newspapers, and mailing lists. We analyzed sociodemographic and environmental variables obtained from a co-built and evidence-based questionnaire. Mental wellbeing was measured by the Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS). Results: We analyzed data from 11,391 (56.6%) out of 20,235 participants who answered the questionnaire. After weighting data on age and gender distributions, 5415 of the respondents were male (47.5%), 5932 were female (52.1%), and 52 (0.5%) registered as other. Multivariate analyses indicated that various factors impacted mental wellbeing. Being female (p < .001), a student (p < .001), disabled (p = .001), or having no access to outdoor space (p = 0.02) was associated with lower WEMWBS scores. Conversely, being employed (p < .001) and having more social contacts (p < .01) were both associated with greater mental wellbeing. Interpretation: We revealed differences in mental wellbeing among the French population at the early stages of global lockdown. Authorities should consider the particular vulnerability of students, persons with disabilities, and those living in constrained housing conditions that could increase the negative impact of lockdown on mental health.


title: COVID-19 Pandemic in Pakistan: Stages and Recommendations

text: We present a real-time forecast of COVID-19 in Pakistan that is important for decision-making to control the spread of the pandemic in the country. The study helps to develop an accurate plan to eradicate the COVID-19 by taking calculated steps at the appropriate time, that are crucial in the absence of a tested medicine. We use four phenomenological mathematical models, namely Discrete Exponential Growth model, the Discrete Generalized Growth model, the Discrete Generalized Logistic Growth, and Discrete Generalize Richards Growth model. Our analysis explains the important characteristics quantitatively. The study leads to understand COVID-19 pandemic in Pakistan in three evolutionary stages, and provides understanding to control its spread in the short time domain and in the long term domain. For the reason the study is helpful in devising the measures to handle the emerging threat of similar outbreaks in other countries.


title: The genomic variation landscape of globally-circulating clades of SARS-CoV-2 defines a genetic barcoding scheme

text: We describe fifteen major mutation events from 2,058 high-quality SARS-CoV-2 genomes deposited up to March 31st, 2020. These events define five major clades (G, I, S, D and V) of globally-circulating viral populations, representing 85.7% of all sequenced cases, which we can identify using a 10 nucleotide genetic classifier or barcode. We applied this barcode to 4,000 additional genomes deposited between March 31st and April 15th and classified successfully 95.6% of the clades demonstrating the utility of this approach. An analysis of amino acid variation in SARS-CoV-2 ORFs provided evidence of substitution events in the viral proteins involved in both host-entry and genome replication. The systematic monitoring of dynamic changes in the SARS-CoV-2 genomes of circulating virus populations over time can guide therapeutic and prophylactic strategies to manage and contain the virus and, also, with available efficacious antivirals and vaccines, aid in the monitoring of circulating genetic diversity as we proceed towards elimination of the agent. The barcode will add the necessary genetic resolution to facilitate tracking and monitoring of infection clusters to distinguish imported and indigenous cases and thereby aid public health measures seeking to interrupt transmission chains without the requirement for real-time complete genomes sequencing.


title: Mortality rate and estimate of fraction of undiagnosed COVID-19 cases in the US in March and April 2020

text: We use a simple model to derive a mortality probability distribution for a patient as a function of days since diagnosis (considering diagnoses made between 25 February and 29 March 2020). The peak of the mortality probability is the 13th day after diagnosis. The overall shape and peak location of this probability curve are similar to the onset-to-death probability distribution in a case study using Chinese data. The total mortality probability of a COVID-19 patient in the US diagnosed between 25 February and 29 March is about 21%. We speculate that this high value is caused by severe under-testing of the population to identify all COVID-19 patients. With this probability, and an assumption that the true probability is 2.4%, we estimate that 89% of all SARS-CoV-2 infection cases were not diagnosed during this period. When the same method is applied to data extended to 25 April, we found that the total mortality probability of a patient diagnosed in the US after 1 April is about 6.4%, significantly lower than for the earlier period. We attribute this drop to increasingly available tests. Given the assumption that the true mortality probability is 2.4%, we estimate that 63% of all SARS-CoV-2 infection cases were not diagnosed during this period (1 - 25 April).


COVID-19 economics - first book hits shelves


No evidence supports the use of ether and chloroform inhalation for treating COVID-19


docid: wgpeicxc

title: Trialstreamer: a living, automatically updated database of clinical trial reports

text: Objective Randomized controlled trials (RCTs) are the gold standard method for evaluating whether a treatment works in healthcare, but can be difficult to find and make use of. We describe the development and evaluation of a system to automatically find and categorize all new RCT reports. Materials and Methods Trialstreamer, continuously monitors PubMed and the WHO International Clinical Trials Registry Platform (ICTRP), looking for new RCTs in humans using a validated classifier. We combine machine learning and rule-based methods to extract information from the RCT abstracts, including free-text descriptions of trial populations, interventions and outcomes (the 'PICO') and map these snippets to normalised MeSH vocabulary terms. We additionally identify sample sizes, predict the risk of bias, and extract text conveying key findings. We store all extracted data in a database which we make freely available for download, and via a search portal, which allows users to enter structured clinical queries. Results are ranked automatically to prioritize larger and higher-quality studies. Results As of May 2020, we have indexed 669,895 publications of RCTs, of which 18,485 were published in the first four months of 2020 (144/day). We additionally include 303,319 trial registrations from ICTRP. The median trial sample size in the RCTs was 66. Conclusions We present an automated system for finding and categorising RCTs. This yields a novel resource: A database of structured information automatically extracted for all published RCTs in humans. We make daily updates of this database available on our website (trialstreamer.robotreviewer.net).


title: Risk of death by age and gender from CoVID-19 in Peru, March-May, 2020

text: Peru implemented strict social distancing measures during the early phase of the epidemic and is now experiencing one of the largest CoVID-19 epidemics in Latin America. Estimates of disease severity are an essential indicator to inform policy decisions about the intensity and duration of interventions needed to mitigate the outbreak. Here we derive delay-adjusted case fatality rates (aCFR) of CoVID-19 in a middle-income country in South America. We used government-reported time series of CoVID-19 cases and deaths stratified by age group and gender. Our estimates as of May 25, 2020, of the aCFR for men and women are 10.8% (95%CrI: 10.5-11.1%) and 6.5% (95%CrI: 6.2-6.8%), respectively, and an overall aCFR of 9.1% (95%CrI: 8.9-9.3%). Our results show that senior individuals are the most severely affected by CoVID-19, particularly men, with aCFR of almost 60% for those aged 80- years. We found that men have a significantly higher cumulative morbidity ratio than women across most age groups (proportion test, p-value< 0.001), with the exception of those aged 0-9 years. The COVID-19 epidemic is imposing a large mortality burden in Peru. Senior individuals, especially those who are older than 70 years of age, are being disproportionately affected by the COVID-19 pandemic.


Lockdown ou vigilância participativa em saúde? Lições da Covid-19/ Lockdown or participatory health surveillance? Lessons from the Covid-19


title: The effectiveness of full and partial travel bans against COVID-19 spread in Australia for travellers from China.

text: Australia implemented a travel ban on China on February 1st 2020. Partial lifting of the ban is being considered, given the decline in incidence of COVID-19 in China. We modelled three scenarios to test the impact of travel bans on epidemic control in Australia. Scenario one was no ban, scenario two was the current ban, scenario three was a partial lifting of the current ban to allow over 100,000 university students to enter Australia, but not tourists. We used disease incidence data from China and air travel passenger movements between China and Australia, derived from incoming passenger arrival cards. We estimated the true incidence of disease in China using data on expected proportion of under-ascertainment of cases. We used an age specific deterministic model divided in 18 age stratified groups to model the epidemic in each scenario. The modelled epidemic with the full ban fitted the observed incidence of cases well. The modelled epidemic of the current ban predicts 57 cases on March 6th in Australia, compared to 66 observed on this date. The modelled impact without a travel ban implemented on February the 1st shows the epidemic would continue for more than a year resulting in more than 2000 cases and about 400 deaths. The impact of a partial lifting of a ban is minimal, and may be safe to consider. Travel restrictions were highly effective for containing the COVID-19 epidemic in Australia and averted a much larger epidemic. The epidemic is still containable if other measures are used in tandem as cases surge in other countries. This research can inform decisions on placing or lifting travel bans as a control measure for the COVID-19 epidemic.


title: COVID-19–Associated Collapsing Focal Segmental Glomerulosclerosis: A Report of 2 Cases

text: Collapsing glomerulopathy is an aggressive form of focal segmental glomerulosclerosis with diverse etiologies The presence of APOL1 high risk genotype is a major risk factor for collapsing glomerulopathy in African Americans Coronavirus disease 2019 (COVID-19) is an emerging pandemic with predominant respiratory manifestations However, kidney involvement is being frequently noted and is associated with higher mortality Currently kidney pathology data in COVID-19 are scant and mostly come from postmortem findings We report two African American patients who developed acute kidney injury and proteinuria in temporal association with COVID-19 Kidney biopsies showed collapsing glomerulopathy, endothelial tubuloreticular inclusions, and acute tubular injury, without evidence by electron microscopy or SARS-CoV-2 ISH of viral infection of kidney cells Both patients had APOL1 high risk genotype We propose that collapsing glomerulopathy represents a novel manifestation of COVID-19 especially in people of African descent with APOL1 risk alleles


title: Sustainable smartphone-based healthcare systems: A systems engineering approach to assess the efficacy of respiratory monitoring apps

text: Recent technological developments along with advances in smart healthcare have been rapidly changing the healthcare industry and improving outcomes for patients. To ensure reliable smartphone-based healthcare interfaces with high levels of efficacy, a system dynamics model with sustainability indicators is proposed. The focus of this paper is smartphone-based breathing monitoring systems that could possibly use breathing sounds as the data acquisition input. This can especially be useful for the self-testing procedure of the ongoing global COVID-19 crisis in which the lungs are attacked and breathing is affected. The method of investigation is based on a systems engineering approach using system dynamics modeling. In this paper, first, a causal model for a smartphone-based respiratory function monitoring is introduced. Then, a systems thinking approach is applied to propose a system dynamics model of the smartphone-based respiratory function monitoring system. The system dynamics model investigates the level of efficacy and sustainability of the system by studying the behavior of various factors of the system including patient wellbeing and care, cost, convenience, user friendliness, in addition to other embedded software and hardware breathing monitoring system design and performance metrics (e.g., accuracy, real-time response, etc.). The sustainability level is also studied through introducing various indicators that directly relate to the three pillars of sustainability. Various scenarios have been applied and tested on the proposed model. The results depict the dynamics of the model for the efficacy and sustainability of smartphone-based breathing monitoring systems. The proposed ideas provide a clear insight to envision sustainable and effective smartphone-based healthcare monitoring systems.


title: Older age is associated with sustained detection of SARS-CoV-2 in nasopharyngeal swab samples

text: PCR testing of nasopharyngeal swab samples is used for the diagnosis of coronavirus disease 2019 (COVID-19) and for determining timing of discharge. The viral load usually declines at convalescent phase, but sometimes remained positive for a long time even after relief of symptoms. In this study, we identified older age is associated with sustained detection of SARS-CoV-2 in nasopharyngeal swab samples.


title: A survey of the psychological status of primary school students who were quarantined at home during the coronavirus disease 2019 epidemic in Hangzhou China

text: Objective: To investigate the presence of social anxiety and depression and the risk factors for them among primary school students who were quarantined at home during the coronavirus disease 2019 (COVID-19) epidemic in Hangzhou China. Methods: A total of 1620 students who were quarantined at home for at least one month were recruited from two primary schools in Hangzhou. Students completed a questionnaire on a mobile App with help from their guardians; the measures included demographic and general information, the Social Anxiety Scale for Children (SASC), and the Depression Self-rating Scale for Children (DSRSC). Results: The mean SASC score of the participants was 3.90{+/-}3.73, which was higher than the mean norm score of Chinese urban children (3.48{+/-}3.47) (P < 0.01). The mean DSRSC score of the participants (5.67{+/-}4.97) was much lower than the mean norm score of Chinese urban children (9.84{+/-}4.73) (P < 0.05). A total of 279 (17.2%) students had social anxiety, with a mean score of 10.41{+/-}2.59, and 102 (6.3%) students had depression, with a mean score of 18.96{+/-}3.89. The following variables were found to be significant risk factors for social anxiety during home quarantine: deterioration of the parent-child relationship, increased conflicts with parents, irregular work and rest, and worrying more about being infected. Deterioration of the parent-child relationship, less physical activity, irregular work and rest, and negative mood during home quarantine were significant risk factors for depression. Conclusion: Primary school students who were quarantined at home during the COVID-19 epidemic were more likely to have social anxiety but less likely to have depressive symptoms. Poor parent-child relationships, irregularity of work and rest, and epidemic-related problems were the main reasons for psychological problems. Families, schools, and social organizations need to pay more attention to the psychological status of primary school students quarantined at home.


title: The clinical and demographical profile of Coronavirus illness: The tale of Tablighi Jamaat and Zaireen in Quarantine / Isolation center at Sukkur and Hyderabad

text: OBJECTIVES: To determine the clinical and demographical profile of corona-virus illness among Tablighi Jamaat and Zaireen kept in quarantine / isolation center at Sukkur and Hyderabad Sindh. METHODS: The cross-sectional descriptive study (late March-2020 to mid of April-2020) was conducted at Diagnostic & Research Laboratory LUMHS Jamshoro / Hyderabad. All the suspected cases for COVID-19 were recruited and screened for corona virus infection. The study explored the data of the suspected and diagnosed (confirmed) case of COVID-2019 (Tablighi Jamaat and Zaireen) reported by Diagnostic Research Laboratory Liaquat University of Medical and Health Sciences (LUMHS) Jamshoro who belonged to various parts of the country in general and province Sindh in particular. All the individuals regardless of age and gender presented either as asymptomatic, critical ill or having non-specific symptoms as fever, flu, cough; sore throat and shortness of breath were screened for COVID-19 by real time PCR after taking informed consent whereas the frequency / percentages (%) and means ±SD computed for study variables. RESULTS: During study period total 920 patients were explored and screened for Corona virus infection. The mean ± SD for age (yrs) of overall population of city Sukkur and Hyderabad was 57.83±8.84 and 59.62±9.72 respectively. The 700 people from Sukkur city was screened and out of them 276 (39.4%) were positive and 424 (60.5) were negative while the cure rate was 245 (88.7%) along with mean ± SD for recovery time was 9.41±2.97. The 220 people from Hyderabad city was screened and out of them 106 (48.1%) were positive and 114 (51.8%) were negative while the cure rate was 106 (100%) along with mean ± SD for recovery time was 11.54±3.42. The majority of cases at both centers were asymptomatic (90%), symptomatic (7%) and critically ill (3%). The mortality accounted for 2.8% cases at Hyderabad isolation center and all were having smoking history and co-morbidities as ischemic heart diseases, diabetes mellitus, obstructive lung disease and cerebrovascular accident whereas no mortality was observed at Sukkur isolation center. CONCLUSION: RT-PCR measure allowed fast, delicate, and explicit discovery of SARS-CoV in biochemical diagnosis. The majority of cases at both centers were asymptomatic while the mortality was identified in 2.8% cases (having co-morbidities) at Hyderabad isolation center whereas no mortality was observed at Sukkur isolation center.


title: Development and Validation of a Diagnostic Nomogram to Predict COVID-19 Pneumonia

text: Background: The COVID-19 virus is an emerging virus rapidly spread worldwide This study aimed to establish an effective diagnostic nomogram for suspected COVID-19 pneumonia patients. METHODS: We used the LASSO aggression and multivariable logistic regression methods to explore the predictive factors associated with COVID-19 pneumonia, and established the diagnostic nomogram for COVID-19 pneumonia using multivariable regression. This diagnostic nomogram was assessed by the internal and external validation data set. Further, we plotted decision curves and clinical impact curve to evaluate the clinical usefulness of this diagnostic nomogram. RESULTS: The predictive factors including the epidemiological history, wedge-shaped or fan-shaped lesion parallel to or near the pleura, bilateral lower lobes, ground glass opacities, crazy paving pattern and white blood cell (WBC) count were contained in the nomogram. In the primary cohort, the C-statistic for predicting the probability of the COVID-19 pneumonia was 0.967, even higher than the C-statistic (0.961) in initial viral nucleic acid nomogram which was established using the univariable regression. The C-statistic was 0.848 in external validation cohort. Good calibration curves were observed for the prediction probability in the internal validation and external validation cohort. The nomogram both performed well in terms of discrimination and calibration. Moreover, decision curve and clinical impact curve were also beneficial for COVID-19 pneumonia patients. CONCLUSION: Our nomogram can be used to predict COVID-19 pneumonia accurately and favourably.


Targeting the SARS-CoV-2 spike


title: RAPID SEROLOGICAL TESTS HAVE A ROLE IN ASYMPTOMATIC HEALTH WORKERS COVID-19 SCREENING

text: Health workers are at high risk for SARS-CoV-2 infection and, if asymptomatic, for transmitting the virus on to fragile cancer patients. We screened 512 health workers of our Cancer Institute with rapid serological test Viva-Diag analyzing, with colorimetric test,IgG/IgM- COVID-19 associated. Five subjects (1%) resulted with Viva-Diag test not-negative for IgM. All of them had rt-PCR SARS-CoV-2 test negative while for 2 out of 5 cases, CLIA analysis confirmed positive IgM expression. In this original study on health workers we demonstrated that Viva-Diag is able to evidence subjects positive for IgM expression. However, discordant results with respect to rt-PCR and CLIA assays clearly refer to further studies to optimize the utilization of the serological test in asymptomatic and in at risk subjects.


title: Predictive Analysis for Social Processes I: Multi-Scale Hybrid System Modeling

text: This two-part paper presents a new approach to predictive analysis for social processes. In Part I, we begin by identifying a class of social processes which are simultaneously important in applications and difficult to predict using existing methods. It is shown that these processes can be modeled within a multi-scale, stochastic hybrid system framework that is sociologically sensible, expressive, illuminating, and amenable to formal analysis. Among other advantages, the proposed modeling framework enables proper characterization of the interplay between the intrinsic aspects of a social process (e.g., the appeal of a political movement) and the social dynamics which are its realization; this characterization is key to successful social process prediction. The utility of the modeling methodology is illustrated through a case study involving the global SARS epidemic of 2002-2003. Part II of the paper then leverages this modeling framework to develop a rigorous, computationally tractable approach to social process predictive analysis.


docid: ycywtpzj

title: Piloting Forensic Tele-Mental Health Evaluations of Asylum Seekers

text: Problem Forensic mental health evaluations can provide critical evidence in the legal cases of individuals seeking asylum and other forms of protected immigration status. While the number of academically affiliated medical human rights programs has increased in recent years, there is still substantial unmet need for pro bono evaluations throughout the United States, especially for individuals in detention. Approach The Mount Sinai Human Rights Program launched its pilot Remote Evaluation Network in September 2019, with the aim to coordinate forensic mental health evaluations by telephone or video call for individuals who are unable to access in-person services. The authors recruited mental health clinicians from across the country, trained them in best practices in conducting forensic evaluations using telehealth platforms, and coordinated pro bono mental health evaluations of individuals seeking immigration relief. Remote forensic services have been a particularly relevant solution in the context of the COVID-19 pandemic. Outcomes The Remote Evaluation Network consists of seventeen active evaluators. From December 2019 to April 2020, the pilot program has coordinated fifteen forensic evaluations of individuals seeking asylum and other forms of protected immigration status in six different states. All clinicians participated in a training module on best practices in conducting forensic evaluations by telephone; respondents to optional pre-and-post-module surveys reported an increase in comfort level with conducting telephonic evaluations after participating in the module. Next Steps We will formally evaluate this pilot program's services by assessing the quality of medico-legal affidavits from telephonic evaluations, tracking legal outcomes and qualitative feedback from attorneys, and investigating the acceptability of telephonic mental health evaluations among legal professionals. Future directions include expansion to new geographies, including individuals affected by the Migrant Protection Protocols or "Remain in Mexico" program.


title: The role of an Orthopaedic Surgeon in the time of Covid-19 Pandemic–a German perspective

text: Covid-19 is a non-orthopaedic disease but is affecting the community of Orthopaedics as much as every part of our daily living. In this Editorial the different aspects of changes in our routine are described, based on the experience of this Editor in Germany. I will try to give you a bit of background information first, as the situation is very much dependent on the specific phase of the pandemic and your place of work. The experience for an Orthopaedic Surgeon in New York or Madrid may differ from that of an Orthopaedic Surgeon in Singapore, or South Korea. As Europe is, at least at the moment, the most affected continent, it hopefully is an interesting topic for all of you. The Covid-19 pandemic is affecting all aspects of our lives, therefore this editorial is divided into 4 sessions: Role as surgeon, as doctor, as teacher, and as family member. Most countries have stopped elective surgeries and by that relegated Orthopaedic surgeons to a minimum of work. Keeping contact to patients with digital tools might be an option to achieve an organised restart after the end of the lock down period and to keep treating patients through that phase. For many Orthopaedic surgeons, the principal task now is being part of an interdisciplinary team that is headed by colleagues from Internal Medicine or Anaesthesiology. Wards from the Orthopaedic department are reorganised as quarantine wards for Covid-19 patients. Worldwide all conferences have been cancelled and nobody knows for how long this will continue. Education now has become fully digital, allowing to present and communicate without real limitations compared to conventional conferences. Some teaching options, such as hands-on workshops, fellowships, etc. are ceased and cannot be replaced by digital options. Due to social distancing families are spending much more time together than before, while some family members, especially the people at risk (elders, ones with a fragile health) cannot be visited for a long time. Get togethers with friends as well as community meetings are completely suspended. For some of them, digital technology is the only option to minimize the problem of social distancing. Overall, it has to be stated, that all parts of our lives as an Orthopaedic Surgeon are affected by the Covid-19 pandemic. As nobody knows how long these restrictions need to remain in place we have to accept them and work on improving this specific situation by following the rules. Hopefully, a vaccine will be developed in the near future, allowing us to return to a “normal” life. Nevertheless, it will never be like it was before.


title: Estimating Lower Bounds for COVID-19 Mortality from Northern Italian Towns

text: For COVID-19 the Infection Fatality Rate or IFR - a crucial variable in epidemiological modeling - is difficult to estimate because many cases are asymptomatic and the overall infection rate is generally not known. Circumstances in the Italian provinces of Milano, Bergamo, Brescia, and Lodi allow estimation of lower bounds for age- and sex-specific all-cause excess mortality (a proxy for IFR) since anecdotal reports indicate some towns were close to fully infected. Using data from ISTAT on mortality from January 1 through April 15 for 2020 and the three preceding years, I estimate excess mortality by sex and age categories (0-14, 15-54, 55-64, 65-74, and 75+ years) while controlling for town-specific mortality that proxies for town-specific infection rate. The 99th percentile from the tail of the town distribution gives a lower-bound estimate for COVID-19 mortality. The overall population-weighted mortality at the 99th percentile is 1.09 percent (95% CI 1.06-1.14). The age- and sex-specific rates vary considerably: for men age 65-74 the estimate is 2.10 percent (95% CI 1.94-2.28) which is 3.5-times higher than men 55-64 and 2.7-times higher than women 65-74.


title: COVID-19 pandemic-related lockdown: response time is more important than its strictness

text: The rapid spread of SARS-CoV-2 and its threat to health systems worldwide have led governments to take acute actions to enforce social distancing. Previous studies used complex epidemiological models to quantify the effect of lockdown policies on infection rates. However, these rely on prior assumptions or on official regulations. Here, we use country-specific reports of daily mobility from people cellular usage to model social distancing. Our data-driven model enabled the extraction of mobility characteristics which were crossed with observed mortality rates to show that: (1) the time at which social distancing was initiated is of utmost importance and explains 62% of the number of deaths, while the lockdown strictness or its duration are not as informative; (2) a delay of 7.49 days in initiating social distancing would double the number of deaths; and (3) the expected time from infection to fatality is 25.75 days and significantly varies among countries.


title: No official help is available - experience of parents and children with congenital heart disease during COVID-19

text: Purpose of the study The purpose was to explore the experience, information, support needs and decision-making of parents with congenital heart disease (CHD) during the COVID-19 crisis. Study design On-line survey design Setting An on-line survey with open/closed questions to explore the experiences of parents of children, as well as children and young people (CYP) with CHD during the COVID-19 crisis Patients Parents of children with CHD and CYP Results 184 parents and 36 CYP completed the survey. Parents worry about the virus (86.4%) vs. CYP (69.4%), whilst (89%) parents are vigilant for symptoms of the virus vs. CYP(69.4%). A thematic analysis of the qualitative comments covered 34 subthemes, forming eight-overarching themes: Virus 1)risk of infection, 2)information, guidance and advice, 3)change in health care provision, and 4)fears and anxieties; Lockdown and isolation 5)psychological and social impact, 6)keeping safe under lockdown, 7)provisions and dependence on others, 8)employment and income. Conclusions Parents and CYP were worried about the virus, although CYP less so. Parents and children however, were frustrated with the lack of specific and paediatric focused information and guidance, expressing disappointment with the adult centric information available. Parents also felt alone, especially with their concerns around the implications of cardiac service suspension and the implication for their childs health. In order to better support children and their families, resources need to be developed to address families and CYP concerns for their health during this pandemic.


title: Interaction between malarial transmission and BCG vaccination with COVID-19 incidence in the world map: A changing landscape human immune system?

text: Background: COVID-19 (Corona virus Disease-2019) is a new public health emergency and is a pandemic currently. Incidence and mortality of COVID-19 vary in different geographical areas. In this study we aimed to analyse the relationship between malaria transmission and BCG vaccination with COVID-19 incidence in the world map. Materials and methods: We collected malaria cases data (World Health Organisation (WHO), 2018), worldwide COVID-19 cases and mortality data (European Centre for Disease Prevention and Control) and data on BCG vaccination. COVID-19 incidence and mortality was compared. Findings: Data on 5316978938 persons from 166 countries were analysed. Malaria incidence rate was negatively correlated with COVID-19 incidence rate (correlation coefficient = -0.513, p<0.001). Malaria free countries had significantly higher number of COVID-19 cases compared to malaria endemic countries. In Europe and Americas, countries, which have higher BCG vaccination coverage, had significantly less mortality per thousand population compared to those with low BCG coverage (median 0.0002 (0-0.0005) vs 0.0029 (0.0002-0.0177), p=0.017). The case fatality ratio of COVID-19 was related nonlinearly to the malaria incidence. Conclusions: The results suggest the changing human immune system as we progress to eliminate parasitic diseases with time. Chloroquine exposure in malaria endemic zones might have a protective effect.


title: Olfactory Dysfunction in Coronavirus Disease 2019 Patients: Observational Cohort Study and Systematic Review

text: BACKGROUND: Olfactory dysfunction (OD) has been reported in coronavirus disease 2019 (COVID-19). However, there are knowledge gaps about the severity, prevalence, etiology, and duration of OD in COVID-19 patients. METHODS: Olfactory function was assessed in all participants using questionnaires and the butanol threshold test (BTT). Patients with COVID-19 and abnormal olfaction were further evaluated using the smell identification test (SIT), sinus imaging, and nasoendoscopy. Selected patients received nasal biopsies. Systematic review was performed according to PRISMA guidelines. PubMed items from January 1, 2020 to April 23, 2020 were searched. Studies that reported clinical data on olfactory disturbances in COVID-19 patients were analyzed. RESULTS: We included 18 COVID-19 patients and 18 controls. Among COVID-19 patients, 12 of 18 (67%) reported olfactory symptoms and OD was confirmed in 6 patients by BTT and SIT. Olfactory dysfunction was the only symptom in 2 patients. Mean BTT score of patients was worse than controls (P = .004, difference in means = 1.8; 95% confidence interval, 0.6–2.9). Sinusitis and olfactory cleft obstruction were absent in most patients. Immunohistochemical analysis of nasal biopsy revealed the presence of infiltrative CD68(+) macrophages harboring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen in the stroma. Olfactory dysfunction persisted in 2 patients despite clinical recovery. Systematic review showed that the prevalence of olfactory disturbances in COVID-19 ranged from 5% to 98%. Most studies did not assess olfaction quantitatively. CONCLUSIONS: Olfactory dysfunction is common in COVID-19 and may be the only symptom. Coronavirus disease 2019-related OD can be severe and prolonged. Mucosal infiltration by CD68(+) macrophages expressing SARS-CoV-2 viral antigen may contribute to COVID-19-related OD.


title: The Prediction for Development of COVID-19 in Global Major Epidemic Areas Through Empirical Trends in China by Utilizing State Transition Matrix Model

text: Background: Since pneumonia caused by coronavirus disease 2019 (COVID-19) broke out in Wuhan, Hubei province, China, tremendous infected cases has risen all over the world attributed to high transmissibility. We managed to mathematically forecast the inflection point (IFP) of new cases in South Korea, Italy, and Iran, utilizing the transcendental model from Hubei and non-Hubei in China. Methods: We extracted data from reports released by the National Health Commission of the People's Republic of China (Dec 31, 2019 to Mar 5, 2020) and World Health Organization (Jan 20, 2020 to Mar 5, 2020) as the training set to deduce the arrival of the IFP of new cases in Hubei and non-Hubei on subsequent days and the data from Mar 6 to Mar 9 as validation set. New close contacts, newly confirmed cases, cumulative confirmed cases, non-severe cases, severe cases, critical cases, cured cases, and death data were collected and analyzed. Using this state transition matrix model, the horizon of the IFP of time (the rate of new increment reaches zero) could be predicted in South Korean, Italy, and Iran. Also, through this model, the global trend of the epidemic will be decoded to allocate international medical resources better and instruct the strategy for quarantine. Results: the optimistic scenario (non-Hubei model, daily increment rate of -3.87%), the relative pessimistic scenario (Hubei model, daily increment rate of -2.20%), and the relatively pessimistic scenario (adjustment, daily increment rate of -1.50%) were inferred and modeling from data in China. Matching and fitting with these scenarios, the IFP of time in South Korea would be Mar 6-Mar 12, Italy Mar 10-Mar 24, and Iran is Mar 10-Mar 24. The numbers of cumulative confirmed patients will reach approximately 20k in South Korea, 209k in Italy, and 226k in Iran under fitting scenarios, respectively. There should be room for improvement if these metrics continue to improve. In that case, the IFP will arrive earlier than our estimation. However, with the adoption of different diagnosis criteria, the variation of new cases could impose various influences in the predictive model. If that happens, the IFP of increment will be higher than predicted above. Conclusion: We can affirm that the end of the burst of the epidemic is still inapproachable, and the number of confirmed cases is still escalating. With the augment of data, the world epidemic trend could be further predicted, and it is imperative to consummate the assignment of global medical resources to manipulate the development of COVID-19.


title: IMPACT OF COVID-19 PANDEMIC ON MENTAL HEALTH OF MEDICAL STUDENTS:A CROSS-SECTIONAL STUDY USING GAD-7 AND PHQ-9 QUESTIONNAIRES

text: Aim: to evaluate anxiety and depression disorders among medical students during COVID-19 pandemic. Methods: cross-sectional study of medical students conducted in May 2020 with questionnaires regarding social and demographic status and GAD-7 for anxiety and PHQ-9 for depression questionnaires. Results: participated 340 (97.98%) students. Average GAD-7 score was 9.18 (M = 9.18; SD = 4.75); average PHQ-9 score was 12.72 (M = 12.72; SD = 6.62). Results indicate a positive significant relationship between GAD-7 and females, and social distancing affecting finances. Using cut-off score of 10 for GAD-7, 157 (46.17%) students were identified with moderated or severe symptoms of anxiety. For PHQ-9 score, using cut-off of 10, 219 (64.41%) students were identified with moderate or severe symptoms of depression; results indicate a positive significant relationship between PHQ-9 and females and between social distancing affecting finances. Conclusion: analysis demonstrated a higher prevalence of moderated and severe anxiety and depression symptoms among medical students during COVID-19 pandemic, significantly among women and on medical students relating financial impairment related to COVID-19 epidemic.


title: Psychological and Behavioral Response to the Coronavirus (COVID-19) Pandemic

text: Background The outbreak of Coronavirus (COVID-19) in Wuhan, China, which began in December 2019, evolved to become a global pandemic. The pandemic, along with the obvious health-related impact, also poses a serious threat to the psychological well-being of individuals and has resulted in significant behavioral changes. We aimed to describe the psycho-behavioral response to this crisis among the population of Karachi, Pakistan, in the month of March 2020. Methods A structured, self-administered questionnaire was constructed, based on previously conducted surveys, assessing the psychological impact and behavioral changes pertaining to COVID-19. Questionnaires were made available online, and were administered to any individual who was a resident of Karachi, during March 2020. Data were analyzed using Statistical Package for Social Sciences (SPSS) version 21.0 (IBM Corp., Armonk, NY) to identify possible risk factors for psychological and behavioral changes. The responses were compared based on gender, age, and level of education, to find possible statistical correlations using chi-square test. Results This research studied data from 400 participants residing in Karachi, Pakistan. The spread of the virus had resulted in subsequent development of fears in the target population, with the majority of the respondents feeling anxious on a daily basis (62.5%). The participants feared going to marketplaces (88.8%), were concerned for the health of their family members (94.5%), and felt under-confident with the current infection control measures (71%). Significantly elevated levels of fear were noted among people >35 years of age. They were more likely to fear for the safety of their health even at home (p=0.06). Meanwhile, increased levels of anxiety due to use of social media among people below 35 years had resulted in avoidance behaviors (p=0.04). There was a higher tendency for graduates to fear for the safety of their health, even at home (p<0.01). In addition, more than three-fourths of our participants had incorporated changes in their behavior to ensure their safety i.e. reduced physical contact (86.5%) and visits to healthcare facilities (74.5%), canceled plans (84.5%), and washing hands more often (87%). Conclusion Our study highlighted the increased anxiety levels that an individual experienced on a regular basis regarding their health, the health of their peers, certain avoidance behaviors as a result of the disease, and behavioral changes of the concerned population. Besides calling attention to this worrisome situation, we also tried to list possible solutions to avert any future distress that may ensue as a result. Hopefully, our study will help the concerned authorities to take measures in order to alleviate the psychological and behavioral impact of COVID-19.


title: Modeling the Dynamics of the COVID-19 Population in Australia: A Probabilistic Analysis

text: The novel Corona Virus COVID-19 arrived on Australian shores around 25 January 2020. This paper presents a novel method of dynamically modeling and forecasting the COVID-19 pandemic in Australia with a high degree of accuracy and in a timely manner using limited data; a valuable resource that can be used to guide government decision-making on societal restrictions on a daily and/or weekly basis. The "partially-observable stochastic process" used in this study predicts not only the future actual values with extremely low error, but also the percentage of unobserved COVID-19 cases in the population. The model can further assist policy makers to assess the effectiveness of several possible alternative scenarios in their decision-making processes.


title: Epidemiological and clinical features of the 2019 novel coronavirus outbreak in China

text: Our manuscript was based on surveillance cases of COVID-19 identified before January 26, 2020. As of February 20, 2020, the total number of confirmed cases in mainland China has reached 18 times of the number in our manuscript. While the methods and the main conclusions in our original analyses remain solid, we decided to withdraw this preprint for the time being, and will replace it with a more up-to-date version shortly. Should you have any comments or suggestions, please feel free to contact the corresponding author.


title: Analysis clinical features of COVID-19 infection in secondary epidemic area and report potential biomarkers in evaluation

text: Objective: Based on the clinical characteristics of infected patients with novel coronavirus in secondary epidemic areas,we aimed to identify potential biomarkers for the evaluation of novel coronavirus-infected patients,guide the diagnosis and treatment of this disease in secondary epidemic areas and provide a reference for the clinical prevention and control of this epidemic situation. Methods: The clinical data of 33 patients with respiratory symptoms caused by the novel coronavirus in Wenzhou city from January 15 to February 12,2020,were thoroughly reviewed. At the onset of the disease,we found that the primary symptoms were fever,cough,fatigue,chest tightness,chest pain and specific blood test results. According to the patients'histories,the patients were divided into two groups: those who spent time in the main epidemic area and those who did not spend time in the main epidemic area. The differences in the clinical manifestations between these two groups were analyzed. Results: The main clinical symptoms of patients infected with novel coronavirus in the secondary epidemic area were respiratory tract ailments and systemic symptoms. After grouping patients based on the presence or absence of residency in or travel history to the main epidemic area, there was no significant difference between the baseline data of these two groups, and there were no significant differences in symptoms and signs between the two groups (P>0.05). Some patients had abnormally increased serum amyloid protein A (SAA). There were statistically significant differences in the leukocyte count/C-reactive protein,monocyte ratio/C-reactive protein,neutrophil count/C-reactive protein,monocyte count/C-reactive protein and hemoglobin/C-reactive protein values between the two groups (P < 0.05). Conclusion: Respiratory tract ailments and systemic symptoms were the primary symptoms of novel coronavirus infection in the secondary epidemic area; these symptoms are not typical. The abnormal increase in serum amyloid protein (SAA) may be used as an auxiliary index for diagnosis and treatment. CRP changes before other blood parameters and thus may be an effective evaluation index for patients with COVID-19 infection.


title: Estimating the cost-of-illness associated with the COVID-19 outbreak in China from January to March 2020

text: Background COVID-19, an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), swept through China in 2019-2020, with over 80,000 confirmed cases reported by end of March 2020. This study estimates the economic burden of COVID-19 in 31 provincial-level administrative regions in China between January and March 2020. Methods The healthcare and societal cost of COVID-19 was estimated using bottom-up approach. The main cost components included identification, diagnosis and treatment of COVID-19, compulsory quarantine and productivity losses for all affected residents in China during the study period. Input data were obtained from government reports, clinical guidelines, and other published literature. The primary outcomes were total health and societal costs. Costs were reported in both RMB and USD (2019 value). Outcomes The total estimated healthcare and societal cost associated with the outbreak is 4.26 billion RMB (0.62 billion USD) and 2,647 billion RMB (383 billion USD), respectively. The main components of routine healthcare costs are inpatient care (41.0%) and medicines (30.9%). The main component of societal costs is productivity losses (99.8%). Hubei province incurred the highest healthcare cost (83.2%) whilst Guangdong province incurred the highest societal cost (14.6%). Interpretation This review highlights a large economic burden of the recent COVID-19 outbreak in China. These findings will aid policy makers in making informed decisions about prevention and control measures for COVID-19. Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.


docid: unvabosp

title: Emergence of RBD mutations in circulating SARS-CoV-2 strains enhancing the structural stability and human ACE2 receptor affinity of the spike protein

text: A novel coronavirus SARS-CoV-2 is associated with the current global pandemic of Coronavirus Disease 2019 (COVID-19). Spike protein receptor-binding domain (RBD) of SARS-CoV-2 is the critical determinant of viral tropism and infectivity. To investigate whether the mutations in the RBD have altered the receptor binding affinity and caused these strains more infectious, we performed molecular dynamics simulations of the binding affinity between the mutant SARS-CoV-2 RBDs to date and the human ACE2 receptor. Among 1609 genomes of global SARS-CoV-2 strains, 32 non-synonymous RBD mutants were identified and clustered into 9 mutant types under high positive selection pressure. Three mutant types (V367F, W436R, and D364Y) emerging in Wuhan, Shenzhen, Hong Kong, and France, displayed higher human ACE2 affinity, and probably higher infectivity. This is due to the enhanced structural stabilization of the RBD beta-sheet scaffold. High frequencies of RBD mutations were identified: V367F from five France and one Hong Kong mutants, 13 V483A and 7 G476S mutants from the U.S.A. This suggested they originated as novel sub-lineages. The enhancement of the binding affinity of the mutant type (V367F) was further validated by the receptor-ligand binding ELISA assay. The molecular dynamics simulations also indicated that it would be difficult for bat SARS-like CoV to infect humans. However, the pangolin CoV is potentially infectious to humans. The analysis of critical RBD mutations provides further insights into the evolutionary history of SARS-CoV-2 under high selection pressure. An enhancement of the SARS-CoV-2 binding affinity to human ACE2 receptor reveals higher infectivity of the mutant strains. Importance A novel coronavirus SARS-CoV-2 has caused the pandemic of COVID-19. The origin of SARS-CoV-2 was associated with zoonotic infections. The spike protein receptor-binding domain (RBD) is identified as the critical determinant of viral tropism and infectivity. Thus, whether the mutations in the RBD of the circulating SARS-CoV-2 strains have altered the receptor binding affinity and caused these strains more infectious, should be paid more attentions to. Here, 32 non-synonymous RBD mutants were identified and clustered into 9 mutant types under high positive selection pressure, suggesting they originated as novel sub-lineages. Three mutant types displayed higher human ACE2 affinity, and probably higher infectivity, one of which (V367F) was validated by wet bench. The RBD mutation analysis provides insights into SARS-CoV-2 evolution. The emergence of RBD mutations with increased human ACE2 affinity reveals higher risk of severe morbidity and mortality during a sustained COVID-19 pandemic, particularly if no effective precautions are implemented.


title: Total COVID-19 Mortality in Italy: Excess Mortality and Age Dependence through Time-Series Analysis

text: We perform a counterfactual time series analysis using two different Data Science methods applied to 2020 mortality data reported from towns in Italy, with data from the previous five years as control. We find an excess mortality that is correlated in time with the COVID-19 reported death rate time series. Our analysis shows good agreement with reported COVID-19 mortality for age<70 years, but an excess in total mortality increasing with age above 70 years, suggesting there is a large population of predominantly old people missing from the official fatality statistics. We estimate that the number of COVID-19 deaths in Italy is 52,000 ± 2000 as of April 18 2020, more than a factor of 2 higher than the official number. The Population Fatality Rate (PFR) has reached 0.22% in the most affected region of Lombardia and 0.57% in the most affected province of Bergamo,which constitutes a lower bound to the Infection Fatality Rate (IFR). We estimate PFR as a function of age, finding a steep age dependence: in Lombardia (Bergamo province) 0.6% (1.7%) of the total population in age group 70-79 died, 1.6% (4.6%) in age group 80-89, and 3.41% (10.2%) in the age group above 90. We combine this with the Test Positivity Rate to estimate the lower bound of 0.84% on the IFR for Lombardia. We observe IFR to trace the Yearly Mortality Rate (YMR) above 60 years, which can be used to estimate the IFR for other regions in the world. We predict an IFR lower bound of 0.5% for NYC and 26% of total COVID-19 mortality arising from the population below 65 years, in agreement with the existing data and several times higher than Lombardia. Combining PFR with the Princess Diamond cruise ship IFR for ages above 70 we estimate the infection rates(IR) of regions in Italy, which peak in Lombardia at 23% (12%-41%, 95% c.l.), and for provinces in Bergamo at 67% (33%-100%, 95% c.l.). This suggests that Bergamo may have reached herd immunity, and that the number of infected people greatly exceeds the number of positive tests, by a factor of 35 in Lombardia.


title: Tracking the Covid-19 pandemic : Simple visualization of the epidemic states and trajectories of select European countries & assessing the effects of delays in official response.

text: We present a self-synchronizing and robust method for comparing the progression of the Covid-19 epidemics among multiple countries. In their growth phase the epidemics show power law rather than exponential law time dependences. They are similar enough for the earlier China outbreak to guide other countries projections. The delayed reaction of European countries is shown to produce a significantly worse outcome compared to China.


title: Spatially Explicit Modeling of 2019-nCoV Epidemic Trend based on Mobile Phone Data in Mainland China

text: IAs of February 11, 2020, all prefecture-level cities in mainland China have reported confirmed cases of 2019 novel coronavirus (2019-nCoV), but the city-level epidemical dynamics is unknown. The aim of this study is to model the current dynamics of 2019-nCoV at city level and predict the trend in the next 30 days under three possible scenarios in mainland China. We developed a spatially explicit epidemic model to consider the unique characteristics of the virus transmission in individual cities. Our model considered that the rate of virus transmission among local residents is different from those with Wuhan travel history due to the self-isolation policy. We introduced a decay rate to quantify the effort of each city to gradually control the disease spreading. We used mobile phone data to obtain the number of individuals in each city who have travel history to Wuhan. This city-level model was trained using confirmed cases up to February 10, 2020 and validated by new confirmed cases on February 11, 2020. We used the trained model to predict the future dynamics up to March 12, 2020 under different scenarios: the current trend maintained, control efforts expanded, and person-to-person contact increased due to work resuming. We estimated that the total infections in mainland China would be 72172, 54348, and 149774 by March 12, 2020 under each scenario respectively. Under the current trend, all cities will show the peak point of daily new infections by February 21. This date can be advanced to February 14 with control efforts expanded or postponed to February 26 under pressure of work resuming. Except Wuhan that cannot eliminate the disease by March 12, our model predicts that 95.4%, 100%, and 75.7% cities will have no new infections by the end of February under three scenarios. The spatial pattern of our prediction could help the government allocate resources to cities that have a more serious epidemic in the next 30 days.


title: Antibody tests in detecting SARS-CoV-2 infection: a meta-analysis

text: With the emergence of SARS-CoV-2 and the associated Coronavirus disease 2019 (COVID-19), there is an imperative need for diagnostic tests that can identify the infection. Although Nucleic Acid Test (NAT) is considered to be the gold standard, serological tests based on antibodies could be very helpful. However, individual studies measuring the accuracy of the various tests are usually underpowered and inconsistent, thus, a comparison of different tests is needed. We performed a systematic review and meta-analysis following the PRISMA guidelines. We conducted the literature search in PubMed, medRxiv and bioRxiv. For the statistical analysis we used the bivariate method for meta-analysis of diagnostic tests pooling sensitivities and specificities. We evaluated IgM and IgG tests based on Enzyme-linked immunosorbent assay (ELISA), Chemiluminescence Enzyme Immunoassays (CLIA), Fluorescence Immunoassays (FIA) and the point-of-care (POC) Lateral Flow Immunoassays (LFIA) that are based on immunochromatography. In total, we identified 38 eligible studies that include data from 7,848 individuals. The analyses showed that tests using the S antigen are more sensitive than N antigen-based tests. IgG tests perform better compared to IgM ones, and show better sensitivity when the samples were taken longer after the onset of symptoms. Moreover, irrespective of the method, a combined IgG/IgM test seems to be a better choice in terms of sensitivity than measuring either antibody type alone. All methods yielded high specificity with some of them (ELISA and LFIA) reaching levels around 99%. ELISA- and CLIA-based methods performed better in terms of sensitivity (90-94%) followed by LFIA and FIA with sensitivities ranging from 80% to 86%. ELISA tests could be a safer choice at this stage of the pandemic. POC tests (LFIA), that are more attractive for large seroprevalence studies show high specificity but lower sensitivity and this should be taken into account when designing and performing seroprevalence studies.


title: Coronavirus Disease-19: Summary of 2,370 Contact Investigations of the First 30 Cases in the Republic of Korea

text: Between January 24(th) and March 10(th), a total of 2,370 individuals had contact with the first 30 cases of COVID-19. There were 13 individuals who contracted COVID-19 resulting in a secondary attack rate of 0.55% (95% CI 0.31–0.96). There were 119 household contacts, of which 9 individuals developed COVID-19 resulting in a secondary attack rate of 7.56% (95% CI 3.7–14.26).


title: Modeling COVID-19 on a network: super-spreaders, testing and containment

text: We use a model of covid-19 spread, an SEIR agent-based model on a graph, which takes into account several important real-life attributes of covid-19: Super-spreaders, realistic epidemiological parameters of the disease, testing and quarantine policies. We provide simulation results and mathematical arguments to argue that certain results of our simulations hold in more general settings. We find that mass-testing is much less effective than testing the symptomatic and contact tracing, and some blend of these with social distancing is required to get suppression. We also find that the fat tail of the degree distribution matters a lot for epidemic growth, and many standard models do not account for this. Additionally, the average reproduction number for individuals is not an upper bound for the effective reproduction number, R. Even with an expectation of less than one new case per person, this model shows that exponential spread is possible. The parameter which closely predicts growth rate is the ratio between 2nd to 1st moments of the degree distribution.


title: Worsening of pre-existing psychiatric conditions during the COVID-19 pandemic

text: This study anonymously examined 2,734 psychiatric patients worldwide for worsening of their pre-existing psychiatric condition during the COVID-19 pandemic. Valid responses mainly from 12 featured countries indicated self-reported worsening of psychiatric conditions in 2/3rd of the patients assessed that was validated through their significantly higher scores on scales for general psychological disturbance, post- traumatic stress disorder, and depression. Female gender, feeling no control of the situation and reporting dissatisfaction with the response of the state during the COVID- 19 pandemic, and reduced interaction with family and friends increased the worsening of pre-existing psychiatric conditions, whereas optimism, ability to share concerns with family and friends and using social media like usual were associated with less worsening. An independent clinical investigation from the USA confirmed worsening of psychiatric conditions during the COVID-19 pandemic based on identification of new symptoms that necessiated clinical interventions such as dose adjustment or starting new medications in more than half of the patients.


SARS-CoV-2 (COVID-19) and Chronic Myeloid Leukemia (CML): a Case Report and Review of ABL Kinase Involvement in Viral Infection


title: A dynamic follow-up of pneumonia caused by coronavirus disease 2019 (COVID-19) on CT Scan

text: Coronavirus disease (COVID-19) broke out in Wuhan, China. It was a highly contagious respiratory disease, the basic reproductive number (RO value) for COVID-19 was reported to be 2.68 with an epidemic doubling time of 6.4 days. In this case report, a 50-yearold man presented with a history of fever and chills. Chest radiographs failed to find any abnormality, and computed tomography (CT) showed ground glass shadow of the upper lobe of the left lung. Real-time polymerase chain reaction (RT-PCR) of the patient’s pharyngeal swab was positive for COVID-19 nucleic acid. The course of the disease developed from mild to severe, then improved and recovered. The patient underwent antiviral drugs, low dose of glucocorticoids, symptomatic treatment, and immunoglobulin for human intravenous injection. We report this long time follow-up case of COVID-19.


title: Traditional Chinese medicine for treatment of COVID-19 based on literature mining of targeting cytokine storm/ 基于干预细胞因子风暴文献挖掘的中医药治疗重症新型冠状病毒肺炎探讨

text: The primary clinical manifestations of coronavirus disease 2019 (COVID-19) are fever, fatigue and dry cough. Several clinical studies reported that some patients with low or medium fever, or even without obvious symptom, rapidly progressed to severe or critical illness, including severe acute respiratory syndrome, septic shock, coagulation disorders and intractable metabolic acidosis. These patients were usually associated with significant elevated serum levels of a profile of cytokines, which is similar to SARS-2003 and MERS-2015, indicating the occurrence of cytokine storm. In the present review, we summarized previous advances in the treatment of severe cases of SARS by using traditional Chinese medicines (TCM), especially those TCM targeting cytokine storm, based on literature mining. By using data mining and network pharmacology, we also investigated underlying mechanisms and biological pathways involved in the inhibitory effects of TCM against cytokine storm. This review not only provides novel insights in the precise application of TCM, appropriate integrative use of TCM in combination with western medicine, but also contributes to the discovery of novel drugs or new therapeutic strategies targeting cytokine storm to suppress progression of COVID-19 and to improve clinical prognosis and outcomes.


Infection control in a dermatology office during a coronavirus epidemic: Let's get down to specifics which includes the auto visitation


title: Fast SARS-CoV-2 detection protocol based on RNA precipitation and RT-qPCR in nasopharyngeal swab samples

text: The SARS-CoV-2 pandemic has evolved far more aggressively in countries lacking a robust testing strategy to identify infected individuals. Given the global demand for fast and reliable diagnosis to determine the carrier individuals, a stock-out scenario for a number of essential reagents/kits used along the diagnostic process has been foreseen by many organizations. Having identified the RNA extraction step as one of the key bottlenecks, we tested several alternatives that avoid the use of commercial kits for this step. The analysis showed that 2-propanol precipitation of the viral RNA, followed by one-step RT-qPCR results in a sensitivity and specificity comparable to that provided currently by automatized systems such as the COBAS 6800 system. Therefore, this simple protocol allows SARS-CoV-2 testing independently of commercial kit providers in a time and cost-effective manner. It can be readily implemented in research and/or diagnostic laboratories worldwide, provided that patient confidentiality and researcher safety are ensured. Scaling up the testing capabilities of hospitals and research facilities will identify larger numbers of infected individuals to paint a clear picture of the COVID-19 prevalence, a pre-requisite for informed policy decision making.


title: Clinical evaluation of a SARS-CoV-2 RT-PCR assay on a fully automated system for rapid on-demand testing in the hospital setting

text: The ongoing SARS-CoV-2 pandemic presents a unique challenge for diagnostic laboratories around the world. Automation of workflows in molecular diagnostics is instrumental for coping with the large number of tests ordered by clinicians, as well as providing fast-tracked rapid testing for urgent cases. In this study we evaluated a SARS-CoV-2 LDT for the NeuMoDx 96 system, a fully automated (sample to result) RT-PCR platform offering random-access capabilities and good clinical performance for SARS-CoV-2 testing.


title: Analytical and Clinical Validation for RT-qPCR detection of SARS-CoV-2 without RNA extraction

text: Background: The recent COVID-19 pandemic has posed an unprecedented challenge to laboratory diagnosis, based on the amplification of SARS-CoV-2 RNA. With global contagion figures exceeding 4 million persons, the shortage of reagents for RNA extraction represents a bottleneck for testing globally. We present the validation results for a RT-qPCR protocol without prior RNA extraction. Because of its simplicity, this protocol is suitable for widespread application in resource-limited settings. Methods: Optimal protocol was selected by comparing RT-qPCR performance under a set of thermal (65{degrees}C, 70{degrees}C, and 95{degrees}C for 5, 10, and 30 minutes) and amplification conditions (3 or 3,5 uL loading volume; 2 commercial RT-qPCR kits with limit of detection below 10 copies/sample) in nasopharyngeal swabs stored at 4{degrees}C in sterile Weise buffer pH 7.2. The selected protocol was evaluated for classification concordance with the standard protocol (automated RNA extraction) in 130 routine samples and in 50 historical samples with Cq values near to the clinical decision limit. Results: Optimal selected conditions were: Thermal shock at 70{degrees}C for 10 minutes, loading 3.5 ul in the RT-qPCR. Prospective evaluation in 130 routine samples showed 100% classification concordance with the standard protocol. The evaluation in historical samples, selected because their Cqs were at the clinical decision limit, showed 94% concordance with our confirmatory-gold standard which includes manual RNA extraction. Conclusions: These results validate the use of this direct RT-qPCR protocol as a safe alternative for SARS CoV-2 diagnosis in case of a shortage of reagents for RNA extraction, with minimal clinical impact.


title: Anaesthetic managment and clinical outcomes of parturients with COVID-19: a multicentre, retrospective, propensity score matched cohort study

text: Objective:To analyse the clinical features of COVID-19 parturients, and to compare anaesthetic regimen and clinical outcomes in parturients with or without COVID-19 undergoing cesarean delivery.Methods: Data were extracted from the electronic medical record of 3 medical institutions in Hubei Province, China, from June 1, 2019 to March 20, 2020 according to inclusion and exclusion criteria. After propensity score matching with demographics, the clinical and laboratory characteristics of parturients with or without COVID-19 were analysed. The anaesthetic regimen and clinical outcomes of themselves and their infants were compared in these two groups of parturients. Results: A total of 1,588 patients without SARS-CoV-2 infection undergoing cesarean delivery were retrospectively included. After achieving a balanced cohort through propensity score matching, 89 patients (COVID-19 group), who were diagnosed with COVID-19 by SARS-CoV-2 nucleic acid test and CT scan matched with 173 patients without COVID-19 (Control group). The SARS-CoV-2 infected parturients in the early stages of COVID-19 outbreak was much more than during the later stage. The main clinical characteristics of parturients with COVID-19 were fever (34.8%), cough (33.7%), an increased plasma CRP (52.8%) and a decreased lymphocyte counting (33.7%). A high rate of emergency and a high incidence of anaesthesia-related complications, such as pharyngalgia, multiple puncture, intraoperative hypotension, nausea, vomiting, vertigo and chills in the COVID-19 parturients. In addition, the parturients with COVID-19 had a long duration of operation and hospital stay, and an increased intraoperative oxytocin utilization and postoperative oxygen therapy. The newborns from the SARS-CoV-2 infected mothers, who received general anaesthesia, had a high risk of Apgar score [≤]8 at 1 and 5 minutes after delivery and a higher rate of neonatal intensive care unit (NICU) admission. Conclusions: Anaesthesia-related complications occur more frequently in the COVID-19 parturients and their newborns have a high risk of distress.


title: Substantial Changes in Nitrate Oxide and Ozone after Excluding Meteorological Impacts during the COVID-19 Outbreak in Mainland China

text: [Image: see text] The COVID-19 outbreak in China led to dramatic changes in human activities resulting from the sudden infection prevention and control measures. Here, we use ground-level observations and model simulations to examine the nationwide spatial–temporal variations of six air pollutants before and after the initiation of First-Level Public Health Emergency Response. The level of ambient NO(2) declined significantly, and in most cities, the decline was dominated by reduced emissions. Meanwhile, the level of O(3) increased significantly during this period, and the nonmeteorological factors explained the increase. For the other air pollutants (PM(2.5), SO(2), and CO), the observed declines on the national scale were obviously affected by the meteorological conditions. In Wuhan, significant declines were found for air pollutants except O(3) and emissions dominated the changes, while in Beijing during the same period, only the level of NO(2) significantly declined. This study clearly shows that the meteorological changes contributed substantially to the observed changes in most air pollutants, and this must be considered in evaluating the impacts of pollutant source changes on air quality during the specific event and in assessing source-oriented risks.


title: Tocilizumab and steroid treatment in patients with severe Covid-19 pneumonia.

text: Introduction Coronavirus disease 2019 (COVID-19) can lead to respiratory failure due to severe immune response. Treatment targeting this immune response might be beneficial but there is limited evidence on its efficacy. The aim of this study was to determine if early treatment of patients with COVID-19 pneumonia with tocilizumab and/or steroids was associated with better outcome. Methods This observational single-center study included patients with COVID-19 pneumonia who were not intubated and received either standard of care (SOC, controls) or SOC plus early (within 3 days from hospital admission) anti-inflammatory treatment. SOC consisted of hydroxychloroquine 400mg bid plus, in those admitted before March 24th, also darunavir/ritonavir. Anti-inflammatory treatment consisted of either tocilizumab (8mg/kg intravenously or 162mg subcutaneously) or methylprednisolone 1 mg/kg for 5 days or both. Failure was defined as intubation or death, and the endpoints were failure-free survival (primary endpoint) and overall survival (secondary) at day 30. Difference between the groups was estimated as Hazard Ratio by a propensity score weighted Cox regression analysis (HROW). Results Overall, 196 adults were included in the analyses. They were mainly male (67.4%), with comorbidities (78.1%) and severe COVID-19 pneumonia (83.7%). Median age was 67.9 years (range, 30-100) and median PaO2/FiO2 200 mmHg (IQR 133-289). Among them, 130 received early anti-inflammatory treatment with: tocilizumab (n=29, 22.3%), methylprednisolone (n=45, 34.6%), or both (n=56, 43.1%). The adjusted failure-free survival among tocilizumab/methylprednisolone/SOC treated patients vs. SOC was 80.8% (95%CI, 72.8-86.7) vs. 64.1% (95%CI, 51.3-74.0), HROW 0.48, 95%CI, 0.23-0.99; p=0.049. The overall survival among tocilizumab/methylprednisolone/SOC patients vs. SOC was 85.9% (95%CI, 80.7-92.6) vs. 71.9% (95%CI, 46-73), HROW 0.41, 95%CI: 0.19-0.89, p=0.025. Conclusion Early adjunctive treatment with tocilizumab, methylprednisolone or both may improve outcomes in patients with COVID-19 pneumonia.


docid: xwghonpl

title: Ignoring scientific advice during the Covid-19 pandemic: Bolsonaro’s actions and discourse


title: Multiple introductions, regional spread and local differentiation during the first week of COVID-19 epidemic in Montevideo, Uruguay

text: Background After its emergence in China in December 2019, the new coronavirus disease (COVID-19) caused by SARS-CoV-2, has rapidly spread infecting more than 3 million people worldwide. South America is among the last regions hit by COVID-19 pandemic. In Uruguay, first cases were detected on March 13 th 2020 presumably imported by travelers returning from Europe. Methods We performed whole-genome sequencing of 10 SARS-CoV-2 from patients diagnosed during the first week (March 16th to 19th) of COVID-19 outbreak in Uruguay. Then, we applied genomic epidemiology using a global dataset to reconstruct the local spatio-temporal dynamics of SARS-CoV-2. Results Our phylogeographic analysis showed three independent introductions of SARS-CoV-2 from different continents. Also, we evidenced regional circulation of viral strains originally detected in Spain. Introduction of SARS-CoV-2 in Uruguay could date back as early as Feb 20th. Identification of specific mutations showed rapid local genetic differentiation. Conclusions We evidenced early independent introductions of SARS-CoV-2 that likely occurred before first cases were detected. Our analysis set the bases for future genomic epidemiology studies to understand the dynamics of SARS-CoV-2 in Uruguay and the Latin America and the Caribbean region.


title: Ophthalmologic evidence against the interpersonal transmission of 2019 novel coronavirus through conjunctiva

text: Background: The emerging 2019 novel coronavirus (2019-nCoV) has pushed several countries into state of emergency all over the world. The possible transmission of 2019-nCoV by conjunctiva is controversial and has substantial public health implications. Methods: A retrospective cohort study was initiated to investigate the possible transmission of 2019-nCoV through aerosol contact with conjunctiva. We enrolled 67 cases of confirmed or suspected cases of novel coronavirus pneumonia (NCP) during 17-28 Jan 2020. Nasopharyngeal and conjunctival swabs were collected for real time RT-PCR analysis to detect 2019-nCoV. Results: 63 patients were identified as laboratory-confirmed NCP and the remaining four were suspected NCP. Conjunctival swab samples from one NCP patient yielded positive PCR results and two NCP patients yielded probable positive PCR results. None of the three patients had ocular symptoms. The only one NCP patient with conjunctivitis as the first symptom had negative conjunctival sac 2019-nCoV test. Conjunctival swab samples from the four suspected cases of NCIP were negative. Conclusion: 2019-nCoV can be detected in the conjunctival sac of patients with NCP. Through clinical analysis, viral transmission via the conjunctival route was not supported by the data. Good clinical protection can effectively cut off the transmission path.


title: When to relax a lockdown? A modelling-based study of testing-led strategies coupled with sero-surveillance against SARS-CoV-2 infection in India

text: India's lockdown against SARS-CoV-2, if lifted without any other mitigations in place, could risk a second wave of infection. A test-and-isolate strategy, using PCR diagnostic tests, could help to minimise the impact of this second wave. Meanwhile, population-level serological surveillance can provide valuable insights into the level of immunity in the population. Using a mathematical model, consistent with an Indian megacity, we examined how seroprevalence data could guide a test-and-isolate strategy, for lifting a lockdown. For example, if seroprevalence is 20% of the population, we show that a testing strategy needs to identify symptomatic cases within 5 - 8 days of symptom onset, in order to prevent a resurgent wave from overwhelming hospital capacity in the city. This estimate is robust to uncertainty in the effectiveness of the lockdown, as well as in immune protection against reinfection. To set these results in their economic context, we estimate that the weekly cost of such a PCR-based testing programme would be less than 2.1% of the weekly economic loss due to the lockdown. Our results illustrate how PCR-based testing and serological surveillance can be combined to design evidence-based policies, for lifting lockdowns in Indian cities and elsewhere.


title: Prognostic factors for COVID-19 pneumonia progression to severe symptom based on the earlier clinical features: a retrospective analysis

text: Background Approximately 15-20% of COVID-19 patients will develop severe pneumonia, about 10 % of which will die if not properly managed. Methods 125 COVID-19 patients enrolled in this study were classified into mild (93 cases) and severe (32 cases) groups, basing on their 3 to 7-days clinical outcomes. Patients' gender, age, comorbid with underlying diseases, epidemiological history, clinical manifestations, and laboratory tests on admission were collected and subsequently analyzed with single-factor and multivariate logistic regression methods. Finally, we evaluate their prognostic values with the receiver operating characteristic curve (ROC) analysis. Results Seventeen factors on admission differed significantly between mild and severe groups. Next, only four factors, including the comorbid with underlying diseases, increased respiratory rate (>24/min), elevated C-reactive protein (CRP >10mg/liter), and lactate dehydrogenase (LDH >250U/liter), were found to be independently associated with the later disease development. Prognostic value analysis by ROC indicated that individual factors could not confidently predict the occurrence of severe pneumonia, but that the combination of fast respiratory rate and elevated LDH significantly increase the predictive confidence (AUC= 0.944, sensitivity= 0.941, and specificity= 0.902). Three- or four-factors combinations, including elevated LDH and fast respiratory rate, further increased the prognostic value. Additionally, measurable serum viral RNA post-admission could independently predict the severe illness occurrence. Conclusions General clinical characteristics and laboratory tests, such as combinations consisting of elevated LDH and fast respiratory rate, and detectable viral RNA in serum post-admission could provide high confident prognostic value for identifying potential severe COVID-19 pneumonia patients.


docid: rwwznlip

title: Anxiety and Suicidality in a Hospitalized Patient with COVID-19 Infection

text: We describe the case of a young man admitted due to mild COVID-19 infection. During his hospitalization in an isolation ward, he had no respiratory distress or fever but developed symptoms consistent with anxiety and insomnia. Despite the appropriate supportive intervention, on hospital day 7, he attempted suicide by jumping from the third-floor ward. The patient underwent urgent surgery and was transferred to a level I trauma center under strict isolation. Our findings emphasize the importance of the mental health aspects of patients treated during the COVID-19 pandemic. LEARNING POINTS: The COVID-19 pandemic requires social distancing, quarantine and isolation, which may precipitate new psychiatric symptoms in people without mental illness or aggravate existing conditions. Mental health service providers, including psychiatrists, clinical psychologists and social workers, should be available in every facility taking care of COVID-19 patients. Health workers treating patients during the COVID-19 pandemic should be aware of symptoms of depression, anxiety, insomnia and/or distress developing in their patients and colleagues.


title: Efficacy and Safety of Hydroxychloroquine and Chloroquine for COVID-19: A systematic review

text: BACKGROUND: Hydroxychloroquine and chloroquine are widely used to treat hospitalized COVID-19 patients primarily based on antiviral activity in in vitro studies. Our objective was to systematically evaluate their efficacy and safety in hospitalized patients with COVID-19. METHODS: We systematically reviewed PubMed, ClinicalTrials.gov, and Medrxviv for studies of hydroxychloroquine and chloroquine in COVID-19 hospitalized patients on April 26, 2020. We evaluated the quality of trials and observational studies using the Jadad criteria and Newcastle Ottawa Scale, respectively. RESULTS: After a review of 175 citations, we included 5 clinical trials (total of 345 patients), 9 observational studies (n = 2529), and 6 additional studies (n = 775) reporting on the QT interval. Three studies reported treatment benefits including two studies reporting benefit on virologic outcomes, which was statistically significant in one study, and another reported significant improvement on cough symptoms. Three studies reported that treatment was potentially harmful, including an significantly increased risk of mortality in two studies and increased need for respiratory support in another. Eight studies were unable to detect improvements on virologic outcomes (n = 3) or pneumonia or transfer to ICU/death (n = 5). The proportion of participants with critical QTc intervals of [≥] 500 ms or an increase of [≥] 60 ms from baseline ranged from 8.3% to 36% (n = 8). One clinical trial and six observational studies were of good quality. The remaining studies were of poor quality. CONCLUSIONS: Our systematic review of reported clinical studies did not identify substantial evidence to support the efficacy of hydroxychloroquine or chloroquine in hospitalized COVID-19 patients and raises questions about potential harm from QT prolongation and increased mortality.


title: Human food consumption patterns concerning COVID-19 pandemic

text: In recent months, despite being aware of the COVID-19 pandemic, many countries faced increasing epidemic of this disease. Nearly all countries tried to decrease human-to-human contact as the principal mode of transmission of SARS-CoV-2. Other modes of transmission also need to be clarified in more depth, especially, the foodborne transmission (FBT). We assessed the effect of animal origin foods (AOF) consumption on the pandemic of COVID-19. For this purpose, we studied the relationship among 20 food supply as independent variables, and the parameter of Total Cases (TC) as dependent variable. The statistical analyses included parametric, non-parametric, frequentist, and Bayesian methods. Results showed a relationship between a group of AOF and TC. So, the role of FBT of COVID-19 should be more significant than previously thought. The possibility of Animal Origin Foodborne Transmission should be taken into more consideration. The perspective is to expand the surveillance of SARS-Cov-2 during the food production chain.


title: SARS-CoV-2 Isolation and Propagation from Turkish COVID-19 patients

text: The novel coronavirus pneumonia, which was named later as Coronavirus Disease 2019 (COVID-19), is caused by the Severe Acute Respiratory Syndrome Coronavirus 2, namely SARS-CoV-2. It is a positive-strand RNA virus that is the seventh coronavirus known to infect humans. The COVID-19 outbreak presents enormous challenges for global health behind the pandemic outbreak. The first diagnosed patient in Turkey has been reported by the Republic of Turkey Ministry of Health on March 11, 2020. Today, over ninety thousand cases in Turkey, and two million cases around the world have been declared. Due to the urgent need for vaccine and anti-viral drug, isolation of the virus is crucial. Here, we report one of the first isolation and characterization studies of SARS-CoV-2 from nasopharyngeal and oropharyngeal specimens of diagnosed patients in Turkey. This study provides an isolation and replication methodology, and cell culture tropism of the virus that will be available to the research communities. Article Summary Scientists have isolated virus from Turkish COVID-19 patients. The isolation, propagation, and plaque and immune response assays of the virus described here will serve in following drug discovery and vaccine testing.


title: Changing transmission dynamics of COVID-19 in China: a nationwide population-based piecewise mathematical modelling study

text: Background: The first case of COVID-19 atypical pneumonia was reported in Wuhan, China on December 1, 2019. Since then, at least 33 other countries have been affected and there is a possibility of a global outbreak. A tremendous amount of effort has been made to understand its transmission dynamics; however, the temporal and spatial transmission heterogeneity and changing epidemiology have been mostly ignored. The epidemic mechanism of COVID-19 remains largely unclear. Methods: Epidemiological data on COVID-19 in China and daily population movement data from Wuhan to other cities were obtained and analyzed. To describe the transmission dynamics of COVID-19 at different spatio-temporal scales, we used a three-stage continuous-time Susceptible-Exposed-Infectious-Recovered (SEIR) meta-population model based on the characteristics and transmission dynamics of each stage: 1) local epidemic from December 1, 2019 to January 9, 2020; 2) long-distance spread due to the Spring Festival travel rush from January 10 to 22, 2020; and 3) intra-provincial transmission from January 23, 2020 when travel restrictions were imposed. Together with the basic reproduction number (R_0) for mathematical modelling, we also considered the variation in infectivity and introduced the controlled reproduction number (R_c) by assuming that exposed individuals to be infectious; we then simulated the future spread of COVID across Wuhan and all the provinces in mainland China. In addition, we built a novel source tracing algorithm to infer the initial exposed number of individuals in Wuhan on January 10, 2020, to estimate the number of infections early during this epidemic. Findings: The spatial patterns of disease spread were heterogeneous. The estimated controlled reproduction number (R_c) in the neighboring provinces of Hubei province were relatively large, and the nationwide reproduction number (except for Hubei) ranged from 0.98 to 2.74 with an average of 1.79 (95% CI 1.77-1.80). Infectivity was significantly greater for exposed than infectious individuals, and exposed individuals were predicted to have become the major source of infection after January 23. For the epidemic process, most provinces reached their epidemic peak before February 10, 2020. It is expected that the maximum number of infections will be approached by the end of March. The final infectious size is estimated to be about 58,000 for Wuhan, 20,800 for the rest of Hubei province, and 17,000 for the other provinces in mainland China. Moreover, the estimated number of the exposed individuals is much greater than the officially reported number of infectious individuals in Wuhan on January 10, 2020. Interpretation: The transmission dynamics of COVID-19 have been changing over time and were heterogeneous across regions. There was a substantial underestimation of the number of exposed individuals in Wuhan early in the epidemic, and the Spring Festival travel rush played an important role in enhancing and accelerating the spread of COVID-19. However, China's unprecedented large-scale travel restrictions quickly reduced R_c. The next challenge for the control of COVID-19 will be the second great population movement brought by removing these travel restrictions.


title: Home collection of nasal swabs for detection of influenza in the Household Influenza Vaccine Evaluation Study

text: Background: Community based studies of influenza and other respiratory viruses (e.g. SARS-COV-2) require laboratory confirmation of infection. During the current COVID-19 pandemic, social distancing guidelines require alternative data collection in order protect both research staff and participants. Home-collected respiratory specimens are less resource intensive, can be collected earlier after symptom onset, and provide a low-contact means of data collection. A prospective, multi-year, community-based cohort study is an ideal setting to examine the utility of home-collected specimens for identification of influenza. Methods: We describe the feasibility and reliability of home-collected specimens for the detection of influenza. We collected data and specimens between October 2014 and June 2017 from the Household Influenza Vaccine Evaluation (HIVE) Study. Cohort participants were asked to collect a nasal swab at home upon onset of acute respiratory illness. Research staff also collected nose and throat swab specimens in the study clinic within 7 days of onset. We estimated agreement using Cohen's kappa and calculated sensitivity and specificity of home-collected compared to staff-collected specimens. Results: We tested 336 paired staff- and home-collected respiratory specimens for influenza by RT-PCR; 150 staff-collected specimens were positive for influenza A/H3N2, 23 for influenza A/H1N1, 14 for influenza B/Victoria, and 31 for influenza B/Yamagata. We found moderate agreement between collection methods for influenza A/H3N2 (0.70) and B/Yamagata (0.69) and high agreement for influenza A/H1N1 (0.87) and B/Victoria (0.86). Sensitivity ranged from 78-86% for all influenza types and subtypes. Specificity was high for influenza A/H1N1 and both influenza B lineages with a range from 96-100%, and slightly lower for A/H3N2 infections (88%). Conclusions: Collection of nasal swab specimens at home is both feasible and reliable for identification of influenza virus infections.


title: Predicting individual risk for COVID19 complications using EMR data

text: Background: The global pandemic of COVID-19 has challenged healthcare organizations and caused numerous deaths and hospitalizations worldwide. The need for data-based decision support tools for many aspects of controlling and treating the disease is evident but has been hampered by the scarcity of real-world reliable data. Here we describe two approaches: a. the use of an existing EMR-based model for predicting complications due to influenza combined with available epidemiological data to create a model that identifies individuals at high risk to develop complications due to COVID-19 and b. a preliminary model that is trained using existing real world COVID-19 data. Methods: We have utilized the computerized data of Maccabi Healthcare Services a 2.3 million member state-mandated health organization in Israel. The age and sex matched matrix used for training the XGBoost ILI-based model included, circa 690,000 rows and 900 features. The available dataset for COVID-based model included a total 2137 SARS-CoV-2 positive individuals who were either not hospitalized (n=1658), or hospitalized and marked as mild (n=332), or as having moderate (n=83) or severe (n=64) complications. Findings: The AUC of our models and the priors on the 2137 COVID-19 patients for predicting moderate and severe complications as cases and all other as controls, the AUC for the ILI-based model was 0.852[0.824-0.879] for the COVID19-based model - 0.872[0.847-0.879].. Interpretation: These models can effectively identify patients at high-risk for complication, thus allowing optimization of resources and more focused follow up and early triage these patients if once symptoms worsen.