title: Systematic review and critical appraisal of prediction models for diagnosis and prognosis of COVID-19 infection

text: Objective To review and critically appraise published and preprint reports of models that aim to predict either (i) presence of existing COVID-19 infection, (ii) future complications in individuals already diagnosed with COVID-19, or (iii) models to identify individuals at high risk for COVID-19 in the general population. Design Rapid systematic review and critical appraisal of prediction models for diagnosis or prognosis of COVID-19 infection. Data sources PubMed, EMBASE via Ovid, Arxiv, medRxiv and bioRxiv until 24th March 2020. Study selection Studies that developed or validated a multivariable COVID-19 related prediction model. Two authors independently screened titles, abstracts and full text. Data extraction Data from included studies were extracted independently by at least two authors based on the CHARMS checklist, and risk of bias was assessed using PROBAST. Data were extracted on various domains including the participants, predictors, outcomes, data analysis, and prediction model performance. Results 2696 titles were screened. Of these, 27 studies describing 31 prediction models were included for data extraction and critical appraisal. We identified three models to predict hospital admission from pneumonia and other events (as a proxy for covid-19 pneumonia) in the general population; 18 diagnostic models to detect COVID-19 infection in symptomatic individuals (13 of which were machine learning utilising computed tomography (CT) results); and ten prognostic models for predicting mortality risk, progression to a severe state, or length of hospital stay. Only one of these studies used data on COVID-19 cases outside of China. Most reported predictors of presence of COVID-19 in suspected patients included age, body temperature, and signs and symptoms. Most reported predictors of severe prognosis in infected patients included age, sex, features derived from CT, C-reactive protein, lactic dehydrogenase, and lymphocyte count. Estimated C-index estimates for the prediction models ranged from 0.73 to 0.81 in those for the general population (reported for all 3 general population models), from 0.81 to > 0.99 in those for diagnosis (reported for 13 of the 18 diagnostic models), and from 0.85 to 0.98 in those for prognosis (reported for 6 of the 10 prognostic models). All studies were rated at high risk of bias, mostly because of non-representative selection of control patients, exclusion of patients who had not experienced the event of interest by the end of the study, and poor statistical analysis, including high risk of model overfitting. Reporting quality varied substantially between studies. A description of the study population and intended use of the models was absent in almost all reports, and calibration of predictions was rarely assessed. Conclusion COVID-19 related prediction models are quickly entering the academic literature, to support medical decision making at a time where this is urgently needed. Our review indicates proposed models are poorly reported and at high risk of bias. Thus, their reported performance is likely optimistic and using them to support medical decision making is not advised. We call for immediate sharing of the individual participant data from COVID-19 studies to support collaborative efforts in building more rigorously developed prediction models and validating (evaluating) existing models. The aforementioned predictors identified in multiple included studies could be considered as candidate predictors for new models. We also stress the need to follow methodological guidance when developing and validating prediction models, as unreliable predictions may cause more harm than benefit when used to guide clinical decisions. Finally, studies should adhere to the TRIPOD statement to facilitate validating, appraising, advocating and clinically using the reported models. Systematic review registration protocol: osf.io/ehc47/, registration: osf.io/wy245


title: COVID-19 Epidemic Analysis using Machine Learning and Deep Learning Algorithms

text: The catastrophic outbreak of Severe Acute Respiratory Syndrome - Coronavirus (SARS-CoV-2) also known as COVID-2019 has brought the worldwide threat to the living society. The whole world is putting incredible efforts to fight against the spread of this deadly disease in terms of infrastructure, finance, data sources, protective gears, life-risk treatments and several other resources. The artificial intelligence researchers are focusing their expertise knowledge to develop mathematical models for analyzing this epidemic situation using nationwide shared data. To contribute towards the well-being of living society, this article proposes to utilize the machine learning and deep learning models with the aim for understanding its everyday exponential behaviour along with the prediction of future reachability of the COVID-2019 across the nations by utilizing the real-time information from the Johns Hopkins dashboard.


Closed positive end-expiratory pressure system: Pre-oxygenation and ventilatory support in COVID-19


title: Replication and Clearance of Respiratory Syncytial Virus : Apoptosis Is an Important Pathway of Virus Clearance after Experimental Infection with Bovine Respiratory Syncytial Virus

text: Human respiratory syncytial virus is an important cause of severe respiratory disease in young children, the elderly, and in immunocompromised adults. Similarly, bovine respiratory syncytial virus (BRSV) is causing severe, sometimes fatal, respiratory disease in calves. Both viruses are pneumovirus and the infections with human respiratory syncytial virus and BRSV have similar clinical, pathological, and epidemiological characteristics. In this study we used experimental BRSV infection in calves as a model of respiratory syncytial virus infection to demonstrate important aspects of viral replication and clearance in a natural target animal. Replication of BRSV was demonstrated in the luminal part of the respiratory epithelial cells and replication in the upper respiratory tract preceded the replication in the lower respiratory tract. Virus excreted to the lumen of the respiratory tract was cleared by neutrophils whereas apoptosis was an important way of clearance of BRSV-infected epithelial cells. Neighboring cells, which probably were epithelial cells, phagocytized the BRSV-infected apoptotic cells. The number of both CD4(+) and CD8+ T cells increased during the course of infection, but the T cells were not found between the epithelial cells of the bronchi up until apoptosis was no longer detected, thus in the bronchi there was no indication of direct contact-dependent T-cell-mediated cytotoxicity in the primary infection.


Designing vaccines computationally


title: Fast isolation of sub-nanomolar affinity alpaca nanobody against the Spike RBD of SARS-CoV-2 by combining bacterial display and a simple single-step density gradient selection

text: Despite the worldwide efforts to avoid disease progression of COVID-19 into a severe acute respiratory syndrome and avoid its severe impact on health systems; the situation remains critical. Effective diagnosis, treatment, and prophylactic measures are required to meet the worldwide demand: recombinant antibodies such as alpaca Nanobodies fulfill these requirements. Here, we develop a fast track for nanobody isolation against the receptor-binding-domain (RBD) SARS-CoV-2 Spike protein following an optimized immunization, efficient construction of the VHH library for E. coli surface display, and single-step selection of high-affinity nanobodies using a simple density gradient centrifugation of the bacterial library. Following this procedure, we isolate and characterize an alpaca Nanobody against Spike RBD of SARS-CoV-2 in the sub-nanomolar range.


docid: ndpuezpo

title: Serology characteristics of SARS-CoV-2 infection since the exposure and post symptoms onset

text: Background Timely diagnosis of SARS-CoV-2 infection is the prerequisite for treatment and preventive quarantine. The serology characteristics and complement diagnosis value of antibody test to RNA test needs to be demonstrated. Method A patient cohort study was conducted at the first affiliated hospital of Zhejiang University, China. Serial sera of COVID-19 patients were collected and total antibody (Ab), IgM and IgG antibody against SARS-CoV-2 were detected. The antibody dynamics during the infection were described. Results The seroconversion rate for Ab, IgM and IgG in COVID-19 patients was 98.8% (79/80), 93.8% (75/80) and 93.8% (75/80), respectively. The first detectible serology marker is total antibody and followed by IgM and IgG, with a median seroconversion time of 15, 18 and 20 day post exposure (d.p.e) or 9, 10 and 12 days post onset, separately. The antibody levels increased rapidly since 6 d.p.o and accompanied with the decline of viral load. For patients in the early stage of illness (0-7d.p.o),Ab showed the highest sensitivity (64.1%) compared to the IgM and IgG (33.3% for both, p<0.001). The sensitivities of Ab, IgM and IgG detection increased to 100%, 96.7% and 93.3% two weeks later, respectively. Conclusions Typical acute antibody response is induced during the SARS-CoV-2 infection. The serology testing provides important complementation to RNA test for pathogenic specific diagnosis and helpful information to evaluate the adapted immunity status of patient. It should be strongly recommended to apply well-validated antibody tests in the clinical management and public health practice to improve the control of COVID-19 infection.


title: Evidence and characteristics of human-to-human transmission of SARS-CoV-2

text: Background: On December 31, 2019, an outbreak of COVID-19 in humans was reported in Wuhan, and then spread fast to other provinces, China. We analyzed data from field investigations and genetic sequencing to describe the evidence and characteristics of human-to-human transmission in Guangdong Province. Methods: A confirmed COVID-19 case was defined if a suspected case was verified with positive of SARS-CoV-2 in throat swabs, nasal swabs, bronchoalveolar lavage fluid (BALF), or endotracheal aspirates by real-time reverse transcriptase polymerase chain reaction assay (RT-PCR) or genetic sequencing. Field investigations were conducted for each confirmed case. Clinical and demographic data of confirmed cases were collected from medical records. Exposure and travel history were obtained by interview. Results: A total of 1,151 confirmed cases were identified as of February 10, 2020 in Guangdong Province, China. Of them, 697 (60.1%) cases were from 234 cluster infections. Two hundred and fourteen (18.6%) were secondary cases, in which 144 cases were from family cluster infections. With the epidemic continuing, although familial cluster events were dominated, community cluster events increased with a nosocomial event. The whole genomes within the same family cluster infections were identical, and presented a few unique single nucleotide variants (SNVs) compared with SARS-CoV-2 identified on December 2019 in Wuhan. Conclusions: We observed evident human-to-human transmissions of SARS-CoV-2 in Guangdong, China. Although most of them were from family cluster infections, community and nosocomial infections were increasing. Our findings indicate that human-to-human transmission risks are transferring from family to community in Guangdong Province.


title: Membrane pore energetics and the pathways to membrane rupture

text: Biological membranes owe their strength and low permeability to the phospholipid bilayers at their core. Membrane strength is determined by the energetics and dynamics of membrane pores, whose tension-dependent nucleation and growth leads to rupture. Creation of nanoscale membrane pores is central to exocytosis, trafficking and other processes fundamental to life that require breaching of secure plasma or organelle membranes, and is the basis for biotechnologies using drug delivery, delivery of genetic material for gene editing and antimicrobial peptides. A prevailing view from seminal electroporation and membrane rupture studies is that pore growth and bilayer rupture are controlled by macroscopically long-lived metastable defect states that precede fully developed pores. It was argued that defect nucleation becomes rate-limiting at high tensions, explaining the exponential tension-dependence of rupture times [E. Evans et al., Biophys. J. 85, 2342-2350 (2003)]. Here we measured membrane pore free energies and bilayer rupture using highly coarse-grained simulations that probe very long time scales. We find no evidence of metastable pore states. At lower tensions, small hydrophobic pores mature into large hydrophilic pores on the pathway to rupture, with classical tension dependence of rupture times. Above a critical tension membranes rupture directly from a small hydrophobic pore, and rupture times depend exponentially on tension. Thus, we recover the experimentally reported regimes, but the origin of the high tension exponential regime is unrelated to macroscopically long-lived pre-pore defects. It arises because hydrophilic pores cannot exist above a critical tension, leading to radically altered pore dynamics and rupture kinetics.


title: Modeling the COVID-19 outbreaks and the effectiveness of the containment measures adopted across countries

text: On March 11, 2020, the World Health Organization declared the COVID-19 outbreak, originally started in China, a global pandemic. Since then, the outbreak has indeed spread across all continents, threatening the public health of numerous countries. Although the Case Fatality Rate (CFR) of COVID-19 is relatively low when optimal level of healthcare is granted to the patients, the high percentage of severe cases developing severe pneumonia and thus requiring respiratory support is worryingly high, and could lead to a rapid saturation of Intensive Care Units (ICUs). To overcome this risk, most countries enacted COVID-19 containment measures. In this study, we use a Bayesian SEIR epidemiological model to perform a parametric regression over the COVID-19 outbreaks data in China, Italy, Belgium, and Spain, and estimate the effect of the containment measures on the basic reproduction ratio R_0. We find that the effect of these measures is detectable, but tends to be gradual, and that a progressive strengthening of these measures usually reduces the R_0 below 1, granting a decay of the outbreak. We also discuss the biases and inconsistencies present in the publicly available data on COVID-19 cases, providing an estimate for the actual number of cases in Italy on March 12, 2020. Lastly, despite the data and model's limitations, we argue that the idea of "flattening the curve" to reach herd immunity is likely to be unfeasible.


title: ‘We have no choice.’ Pandemic forces polio eradication group to halt campaigns

text: Going door-to-door to deliver the oral polio vaccine would put both communities and health workers at risk of COVID-19 The COVID-19 pandemic is imperiling the worldwide, 3-decade drive to wipe out polio In an unprecedented move, the Global Polio Eradication Initiative (GPEI) has recommended suspending polio vaccination campaigns to help stop the spread of the novel coronavirus On 24 March, GPEI’s leadership called on all countries to postpone until at least the second half of this year both mass campaigns to boost immunity to the polio virus and the targeted campaigns underway in Africa to stop outbreaks sparked by the live virus vaccine itself


title: Pediatric Coronavirus Disease 2019 and Radiographic Screening: Identification of Patients at Risk

text: As the coronavirus disease 2019 (COVID-19) pandemic continues globally, there are an increasing number of pediatric cases Since the initial symptoms of COVID-19 may overlap and co-exist with other respiratory infections typically affecting children, this review examines the use of computed tomography as a diagnostic and management tool Children with preexisting conditions may be particularly prone to a more severe course This study reviews and analytically summarizes the findings typically associated with severe acute respiratory syndrome coronavirus 2 in contrast with other more usual lower respiratory tract infections


title: How much leeway is there to relax COVID-19 control measures?

text: Following successful widespread non-pharmaceutical interventions aiming to control COVID-19, many jurisdictions are moving towards reopening economies and borders. Given that little immunity has developed in most populations, re-establishing higher contact rates within and between populations carries substantial risks. Using a Bayesian epidemiological model, we estimate the leeway to reopen in a range of national and regional jurisdictions that have experienced different COVID-19 epidemics. We estimate the risks associated with different levels of reopening and the likely burden of new cases due to introductions from other jurisdictions. We find widely varying leeway to reopen, high risks of exceeding past peak sizes, and high possible burdens per introduced case per week, up to hundreds in some jurisdictions. We recommend a cautious approach to reopening economies and borders, coupled with strong monitoring for changes in transmission.


title: Investigating duration and intensity of Covid-19 social-distancing strategies

text: The exponential character of the recent Covid-19 outbreak requires a change in strategy from containment to mitigation. Meanwhile, most countries apply social distancing with the objective to keep the number of critical cases below the capabilities of the health care system. Due to the novelty and rapid spread of the virus, an a priori assessment of this strategy was not possible. In this study, we present a model-based systems analysis to assess the effectiveness of social distancing measures in terms of intensity and duration of application. Results show a super-linear scaling between intensity (percent contact reduction) and required duration of application to have an added value (lower fatality rate). This holds true for an effective reproduction of R > 1 and is reverted for R < 1. If R is not reduced below 1, secondary effects of required long-term isolation are likely to unravel the added value of disease mitigation. We recommend an extinction strategy implemented by intense countermeasures.


title: On Identifying and Mitigating Bias in the Estimation of the COVID-19 Case Fatality Rate

text: The relative case fatality rates (CFRs) between groups and countries are key measures of relative risk that guide policy decisions regarding scarce medical resource allocation during the ongoing COVID-19 pandemic. In the middle of an active outbreak when surveillance data is the primary source of information, estimating these quantities involves compensating for competing biases in time series of deaths, cases, and recoveries. These include time- and severity- dependent reporting of cases as well as time lags in observed patient outcomes. In the context of COVID-19 CFR estimation, we survey such biases and their potential significance. Further, we analyze theoretically the effect of certain biases, like preferential reporting of fatal cases, on naive estimators of CFR. We provide a partially corrected estimator of these naive estimates that accounts for time lag and imperfect reporting of deaths and recoveries. We show that collection of randomized data by testing the contacts of infectious individuals regardless of the presence of symptoms would mitigate bias by limiting the covariance between diagnosis and death. Our analysis is supplemented by theoretical and numerical results and a simple and fast open-source codebase at https://github.com/aangelopoulos/cfr-covid-19 .


docid: ktwqlubw

title: Novel Coronavirus Disease: A delicate balancing act between health and the economy

text: The emergence of the deadly novel Coronavirus Disease (COVID-19) has resuscitated global attention on the state of health governance and well-being of citizens. Worldwide, countries are in dire dilemma of safeguarding the health of their citizens and equally salvaging economy, arising from the social distancing and lockdown strategies, which affects negatively the economic activities. This paper examines the intricate balance between health and the economy in the wake of the Covid-19 pandemic and the policy options needed to assist countries to implement strategies to protect the health of their citizens and promote economic recovery in this unprecedented global crisis situation. There is need for a coordinated public-private sector partnership in the recovery plan of each country, taking into account their contextual and country specific health system and economy, but not discarding the universal application thereof. Global, regional, national geo-political and public health collaboration is needed to save the world from COVID-19 catastrophic consequences.


title: Meta-analysis of transcriptomes of SARS-Cov2 infected human lung epithelial cells identifies transmembrane serine proteases co-expressed with ACE2 and biological processes related to viral entry, immunity, inflammation and cellular stress

text: The COVID-19 pandemic resulting from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which emerged in December 2019 in the Chinese city of Wuhan in the province Hubei has placed immense burden on national economies and global health. At present neither vaccination nor therapies are available although several antiviral agents such as remdesivir, originally an Ebola drug, nelfinavir, an HIV-1 protease inhibitor and other drugs such as lopinavir have been evaluated. Here, we performed a meta-analysis of RNA-sequencing data from three studies employing human lung epithelial cells. Of these one focused on lung epithelial cells infected with SARS-CoV-2. We aimed at identifying genes co-expressed with angiotensin I converting enzyme 2 (ACE2) the human cell entry receptor of SARS-CoV-2, and unveiled several genes correlated or inversely correlated with high significance, among the most significant of these was the transmembrane serine protease 4 (TMPRSS4). Serine proteases are known to be involved in the infection process by priming the virus spike protein. Pathway analysis revealed papilloma virus infection amongst the most significantly correlated pathways. Gene Ontologies revealed regulation of viral life cycle, immune responses, pro-inflammatory responses-several interleukins such as IL6, IL1, IL20 and IL33, IFI16 regulating the interferon response to a virus, chemo-attraction of macrophages, last and not least cellular stress resulting from activated Reactive Oxygen Species. We believe that this dataset will aid in a better understanding of the molecular mechanism(s) underlying COVID-19.


title: Estimating the effect of physical distancing on the COVID-19 pandemic using an urban mobility index

text: Governments around the world are implementing population-wide physical distancing measures in an effort to control transmission of COVID-19, but metrics to evaluate their effectiveness are not readily available. We used a publicly available mobility index based on the relative frequency of trips planned in a popular transit application to evaluate the effect of physical distancing on infection growth rates and reproductive number in 34 states and countries. We found that a 10% decrease in relative mobility in the 2nd week of March was associated with a 11.8% relative decrease (exp(β) = 0.882; 95% CI: 0.822, 0.946) in the average daily growth rate in the fourth week of March and a change in the instantaneous reproductive number of -0.054 (95% CI: 0.097, -0.011) in the same period. Our analysis demonstrates that decreases in urban mobility were predictive of declines in epidemic growth at national or sub-national scales. Mobility metrics offer an appealing method to calibrate population-level physical distancing policy and implementation.


title: COVID-19 Modelling: the Effects of Social Distancing

text: The purpose of this article is to reach all those who find it difficult to become well informed about the repercussions of a lockdown strategy to tackle the COVID-19 pandemic and to spark discussion and thought. Here we use simple stochastic simulations to evaluate different approaches taken to tackle the crisis, along with the efficiency they will hold and the number of casualties they may incur. It is clear that the less strict the social distancing the more time it will take for life to return to normal, and the more lives will be at risk. This is shown through simulations formed by an open sourced code, which allows evaluation of the outcomes from different intervention scenarios or conditions.


title: The projected impact of mitigation and suppression strategies on the COVID-19 epidemic in Senegal: A modelling study

text: Background: Physical distancing measures that reduce social contacts have formed a key part of national COVID-19 containment and mitigation strategies. Many Sub-Saharan African nations are now facing increasing numbers of cases of COVID-19 and there is a need to understand what levels of measures may be required to successfully reduce transmission. Methods: We collated epidemiological data along with information on key COVID-19 specific response policies and health system capacity estimates for services needed to treat COVID-19 patients in Senegal. We calibrated an age-structured SEIR model to these data to capture transmission dynamics accounting for demography, contact patterns, hospital capacity and disease severity. We simulated the impact of mitigation and suppression strategies focussed on reducing social contact rates. Results: Senegal acted promptly to contain the spread of SARS-CoV-2 and as a result has reduced the reproduction number from 1.9 (95% CI 1.7-2.2) to 1.3 (95% CI 1.2-1.5), which has slowed but not fully interrupted transmission. We estimate that continued spread is likely to peak in October, and to overwhelm the healthcare system with an estimated 77,400 deaths(95% CI 55,270-100,700). Further reductions in contact rates to suppress transmission (Rt<1) could significantly reduce this burden on healthcare services and improve overall health outcomes. Conclusions: Our results demonstrate that Senegal has already significantly reduced transmission. Enhanced physical distancing measures and rapid scale up of hospital capacity is likely to be needed to reduce mortality and protect healthcare infrastructure from high levels of demand.


title: Non-COVID-19 Deaths After Social Distancing in Norway

text: Lay persons and policy makers have speculated on how the imposition of social distancing to reduce SARS CoV-2 (severe acute respiratory syndrome coronavirus 2) infection has affected non-COVID-19 (coronavirus disease of 2019) deaths. No rigorous estimation of the effect appears in the scholarly literature. We use time-series methods to compare non-COVID-19 deaths observed in Norway before and during the epidemic to those expected from non-COVID-19 deaths in Sweden as well as from the history of Norwegian mortality trends. We find that in the first 8 weeks after the divergence between Swedish and Norwegian policies (the only period for which dependable data can be had) approximately 650 fewer Norwegians died than expected.


docid: bsgqsdbx

title: Clinical and immunologic features in severe and moderate forms of Coronavirus Disease 2019

text: Background Since late December, 2019, an outbreak of pneumonia cases caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and continued to spread throughout China and across the globe. To date, few data on immunologic features of Coronavirus Disease 2019 (COVID-19) have been reported. Methods In this single-centre retrospective study, a total of 21 patients with pneumonia who were laboratory-confirmed to be infected with SARS-CoV-2 in Wuhan Tongji hospital were included from Dec 19, 2019 to Jan 27, 2020. The immunologic characteristics as well as their clinical, laboratory, radiological features were compared between 11 severe cases and 10 moderate cases. Results Of the 21 patients with COVID-19, only 4 (19%) had a history of exposure to the Huanan seafood market. 7 (33.3%) patients had underlying conditions. The average age of severe and moderate cases was 63.9 and 51.4 years, 10 (90.9%) severe cases and 7 (70.0%) moderate cases were male. Common clinical manifestations including fever (100%, 100%), cough (70%, 90%), fatigue (100%, 70%) and myalgia (50%, 30%) in severe cases and moderate cases. PaO2/FiO2 ratio was significantly lower in severe cases (122.9) than moderate cases (366.2). Lymphocyte counts were significantly lower in severe cases (7000 million/L) than moderate cases (11000 million/L). Alanine aminotransferase, lactate dehydrogenase levels, high-sensitivity C-reactive protein and ferritin were significantly higher in severe cases (41.4 U/L, 567.2 U/L, 135.2 mg/L and 1734.4 ug/L) than moderate cases (17.6 U/L, 234.4 U/L, 51.4 mg/L and 880.2 ug /L). IL-2R, TNF-α and IL-10 concentrations on admission were significantly higher in severe cases (1202.4 pg/mL, 10.9 pg/mL and 10.9 pg/mL) than moderate cases (441.7 pg/mL, 7.5 pg/mL and 6.6 pg/mL). Absolute number of total T lymphocytes, CD4+T cells and CD8+T cells decreased in nearly all the patients, and were significantly lower in severe cases (332.5, 185.6 and 124.3 million/L) than moderate cases (676.5, 359.2 and 272.0 million/L). The expressions of IFN-γ by CD4+T cells tended to be lower in severe cases (14.6%) than moderate cases (23.6%). Conclusion The SARS-CoV-2 infection may affect primarily T lymphocytes, particularly CD4+T cells, resulting in significant decrease in number as well as IFN-γ production, which may be associated with disease severity. Together with clinical characteristics, early immunologic indicators including diminished T lymphocytes and elevated cytokines may serve as potential markers for prognosis in COVID-19.


title: A Case Report of Rapidly Lethal Acute Respiratory Distress Syndrome Secondary to Coronavirus Disease 2019 Viral Pneumonia

text: As of April 2020, the coronavirus 2019 (COVID-19) pandemic has resulted in more than 210,000 deaths globally. The most common cause of death from COVID-19 is acute respiratory failure. We report the case of a 78-year-old female with a history of hypertension, cerebrovascular accident (CVA), type 2 diabetes mellitus, and sarcoidosis, who presented to the emergency department with one day of dyspnea. The patient experienced a rapid decline in respiratory function and was intubated in the intensive care unit (ICU), meeting the Berlin criteria for severe acute respiratory distress syndrome (ARDS). Chest radiography revealed diffuse bilateral coalescent opacities, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA swab test was positive for COVID-19. The patient experienced acute kidney injury with uptrending creatinine levels and remained lethargic and unresponsive throughout her ICU stay, suggestive of potential hypoxic brain injury. In light of the patient’s poor clinical status, age, and significant comorbidities, prognosis was conveyed about medical futility and patient’s family agreed to terminal extubation and the patient expired peacefully, exactly one week from hospital admission. This case report highlights the speed at which severe ARDS can present and contribute to end-organ dysfunction in COVID-19 patients.


title: The origin and early spread of SARS-CoV-2 in Europe

text: The investigation of migratory patterns of the SARS-CoV-2 pandemic before border closures in Europe is a crucial first step towards an in-depth evaluation of border closure policies. Here we analyze viral genome sequences using a phylodynamic model with geographic structure to estimate the origin and spread of SARS-CoV-2 in Europe prior to border closures. Based on SARS-CoV-2 genomes, we reconstruct a partial transmission tree of the early pandemic, including inferences of the geographic location of ancestral lineages and the number of migration events into and between European regions. We find that the predominant lineage spreading in Europe has a most recent common ancestor in Italy and was probably seeded by a transmission event in either Hubei or Germany. We do not find evidence for preferential migration paths from Hubei into different European regions or from each European region to the others. Sustained local transmission is first evident in Italy and then shortly thereafter in the other European regions considered. Before the first border closures in Europe, we estimate that the rate of occurrence of new cases from within-country transmission was within the bounds of the estimated rate of new cases from migration. In summary, our analysis offers a view on the early state of the epidemic in Europe and on migration patterns of the virus before border closures. This information will enable further study of the necessity and timeliness of border closures.


title: Associations of exercise and social support with mental health during quarantine and social-distancing measures during the COVID-19 pandemic: A cross-sectional survey in Germany

text: Introduction: Social distancing and quarantine measures applied during the COVID-19 pandemic might result in mental health problems. In this cross-sectional study we examined if perceived social support, exercise in minutes per week and change in exercise are protective factors regarding symptoms of depression, anxiety, and sleeping disorders. Method: In April 2020, n = 4271 German adults completed an online survey including mental health questionnaires regarding depression (PHQ-D), anxiety (PHQ-D) and sleep (PSQI), as well as questionnaires related to protective factors such as exercise (BSA-F), physical activity-related health competence (PAHCO) and social support (F-SozU). Results: Complete case analysis (n = 3700; mean age 33.13 {+/-} 11.73 years, 78.6 % females) resulted in elevated prevalence of depressive disorder (31.4%), panic disorder (5.7%) and other anxiety disorders (7.4%). 58.3% reported symptoms of insomnia. Three separate models of multiple regression were conducted. Perceived social support was associated with lower values of anxiety (beta = -0.10; t(19) = -6.46; p >0.001), lower values of depressive symptoms (beta = -0.22; t(19) = -15.71; p < .001) and lower values of sleeping disorder symptoms (beta = -0.15; t(19) = -9.55; p < .001). Change towards less exercise compared to the time before Covid-19 was associated with and higher values of anxiety (beta = -0.05; t(19) = -2.85; p= .004), higher values of depressive symptoms (beta = -0.08; t(19) = -5.69; p < .001), and higher values of sleeping disorder symptoms (beta = -0.07; t(19) = -4.54; p < .000). Post-hoc analysis (ANOVAs) revealed that a change towards less exercise was significantly associated with more depressive, anxiety and sleeping disorder symptoms whereas a positive change was not. No significant association was found for exercise in minutes per week for all outcomes. Conclusion: The COVID-19 pandemic seems to have a negative impact on mental health in the German population. Social Support and a stable amount of exercise might attenuate these negative mental health consequences. Ongoing monitoring of the impact of the pandemic on mental health and possible protective factors is needed in order to create a basis for the development of appropriate prevention and intervention measures.


title: Mortality from COVID-19 in 12 countries and 6 states of the United States

text: Importance: Reliable estimates of COVID-19 mortality are crucial to aid control strategies and to assess the effectiveness of interventions. Objective: Project COVID-19 mortality trends to October 1, 2020, in 12 countries or regions that constitute >90% of the global COVID-19 deaths reported as of April 12, 2020. Design, Setting, and Participants: The Global COVID-19 Assessment of Mortality (GCAM) is an open, transparent, and continuously updated (www.cghr.org/covid) statistical model that combines actual COVID-19 mortality counts with Bayesian inference to forecast COVID-19 deaths, the date of peak deaths, and the duration of excess mortality. The analyses covered a total of 700 million population above age 20 in 12 countries or regions: USA; Italy; Spain; France; UK; Iran; Belgium; a province of China (Hubei, which accounted for 90% of reported Chinese deaths); Germany; the Netherlands; Switzerland; and Canada; and six US states: New York, New Jersey, Michigan, Louisiana, California, and Washington. Results: Forecasted deaths across the 12 current high-burden countries sum 167,000 to 593,000 (median 253,000). The trajectory of US deaths (49,000-249,000 deaths; median 86,000)- over half of which are expected in states beyond the initial six states analysed in this study- will have the greatest impact on the eventual total. Mortality ranges are 25,000-109,000 (median 46,000) in the UK; 23,000-31,000 (median 26,000) in Italy; 21,000-37,000 (median 26,000) in France and 21,000-32,000 (median 25,000) in Spain. Estimates are most precise for Hubei, China, where the epidemic curve is complete, and least precise in California, where it is ongoing. New York has the highest cumulative median mortality rate per million (1135), about 12-fold that of Germany. Mortality trajectories are notably flatter in Germany, California, and Washington State, each of which took physical distancing and testing strategies seriously. Using past country-specific mortality as a guide, GCAM predicts surge capacity needs, reaching more than twice existing capacity in a number of places., In every setting, the results might be sensitive to undercounts of COVID-19 deaths, which are already apparent. Conclusion and Relevance: Mortality from COVID-19 will be substantial across many settings, even in the best case scenario. GCAM will provide continually updated and increasingly precise estimates as the pandemic progresses.


docid: nangvcxn

title: Self(ie)-governance_ Technologies of intimate surveillance in India under COVID19

text: This commentary examines the role of the ‘selfie’ as central to the teleological management of the COVID-19 crisis in India. It suggests that the incorporation of the self(ie) within the technologies of quarantine apps is a simulacrum of intimate surveillance that seeks to experiment in the present in order to extend its reach into the visual governance of intimate domesticity in the future.


title: Preprint server use in kidney disease research: a rapid review

text: Purpose of review: Preprint servers including arXiv and bioRxiv have disrupted the scientific communication landscape by providing rapid access to pre-peer reviewed research. MedRxiv is a recently launched free online repository for preprints in the health sciences. We sought to summarize potential benefits and risks to preprint server use, from both the researcher and end-user perspective, and evaluate the uptake of preprint servers in the nephrology community. Sources of Information: We performed a rapid review of articles describing preprint servers and their use. We approached the 20 highest impact nephrology journals regarding their policy towards the use of preprint servers. We evaluated the average time from study completion to publication of impactful articles in nephrology. Finally, we evaluated the number of nephrology articles submitted to preprint servers. Findings: To date over 600 kidney-related articles have been uploaded to bioRxiv and medRxiv. The average time from study completion to publication was over 10 months. 16 of the top 20 nephrology journals currently accept research submitted to a preprint server. Transparency and collaboration, visibility and recognition, and rapid dissemination of results were identified as benefits of preprint servers. Concerns exist regarding the potential risk of non-peer reviewed medical research being publicly available. Limitations: Preprint servers remain a recent phenomenon in health sciences and their long-term impact on the medical literature remains to be seen. Implications: The quantity of research submitted to preprint servers is likely to continue to grow. The model for dissemination of research results will need to adapt to incorporate preprint servers.


title: ACE2 polymorphisms as potential players in COVID-19 outcome

text: The clinical condition COVID-19, caused by SARS-CoV-2, was declared a pandemic by the WHO in March 2020. Currently, there are more than 5 million cases worldwide, and the pandemic has increased exponentially in many countries, with different incidences and death rates among regions/ethnicities and, intriguingly, between sexes. In addition to the many factors that can influence these discrepancies, we suggest a biological aspect, the genetic variation at the viral S protein receptor in human cells, ACE2 (angiotensin I-converting enzyme 2), which may contribute to the worse clinical outcome in males and in some regions worldwide. We performed exomics analysis in native and admixed South American populations, and we also conducted in silico genomics databank investigations in populations from other continents. Interestingly, at least ten polymorphisms in coding, noncoding and regulatory sites were found that can shed light on this issue and offer a plausible biological explanation for these epidemiological differences. In conclusion, ACE2 polymorphisms should influence epidemiological discrepancies observed among ancestry and, moreover, between sexes.


title: An agent based modelling approach to study lockdown efficacy for infectious disease spreads

text: We sought to simulate lockdown scenarios using an Agent Based Modelling (ABM) strategy, which is a new modelling paradigm that seeks to simulate the actions and interactions of autonomous agents within an environment. The spread of infectious viral diseases occur over a connected social network. Specifically, the goal was to understand the effect of network topology and lockdown strategies on disease spreading dynamics. To explore the effect of topology we assumed the social network over which the disease spreads to have small-world or scale-free properties characterized by a rewiring probability and degree distribution respectively. Lockdowns were simulated as intervention strategies that modified the spreading dynamics of infection over a given graph structure through changes in properties of agent interaction. Lockdown efficacy was assessed by the maximum number of infections recorded during a simulation run. Thereafter, lockdown efficacy was evaluated as a function of lockdown start times and duration. Thus, we propose that ABM approach can be used to assess various lockdown strategies that aim to prevent breakdown of medical infrastructure while accounting for realistic social network configurations specific to a local population.


title: Relationship between COVID-19 death toll doubling time and national BCG vaccination policy

text: In this manuscript, we showed a statistically significant difference of the doubling times of the death toll between the group of countries with national universal Bacillus Calmette-Guerin (BCG) vaccination and the group without it for recent years. Based on a statistical test, the distributions of the doubling time of these two groups were significantly different (p=0.007). Miller et al. reported the relationship between BCG vaccination and mortality for COVID-19 based on deaths per million inhabitants. However, they did not take into account the differences in COVID-19 detection rates among the countries and the epidemic stages of the countries. Therefore we used a doubling time of the death toll as a more stable indicator instead. We also investigated the dependency of the BCG strains. Among the 42 BCG-vaccinated countries, the median doubling time of the eight countries using "Tokyo 172-1" strain at least partially (Japan, Iraq, Malaysia, South Korea, Philippines, Saudi Arabia, Pakistan, and Bangladesh) was 7.2 days, and that of the other 34 vaccinated countries was 5.5 days. Their distributions were also significantly different (p=0.026).


COVID-19: Cultural Predictors of Gender Differences in Global Prevalence Patterns


title: Novel coronavirus (Covid-19)-a critical review

text: No one has even imagined that infection in the respiratory system in the form of pneumonia because of novel coronavirus (SARS-CoV2) in small town of China, Wuhan during end of December in the year 2019 will come out as an extremely communicable infection. The World Health Organization (WHO) has acknowledged the current epidemic as a threat to whole population worldwide. At present, still we have not reached the advanced levels of research to treat and control this contagious disease. Due to lack of information about the pathogenesis and proliferation pathways of this novel corona virus, whole world is looking forward for its exact prophylaxis. On the basis of recent proofs provided by review and research articles from various gen-uine sources, we tried thoroughly to summarize the various factors regarding COVID-19 like its epidemiology, clinical characteristics, diagnosis, treatment and prevention. Through this review we have made an effort to present a com-mon conceptual literature on coronavirus to help community to fight against this dangerous virus, and will hope that this review will be a source of refer-ence to young researchers for advanced studies.


title: Association between rRT-PCR test results upon admission and outcome in hospitalized chest CT-Positive COVID-19 patients; a provincial retrospective cohort with active follow-up

text: Background − The Covid−19 pandemic imposed the most devastating challenge on healthcare systems worldwide. Iran was among the first countries that had to confront serious shortages in RT−PCR testing for SARS−CoV−2 and ventilators availabilities throughout the COVID−19 outbreak. This study aimed to investigate the clinical course of hospitalized COVID−19 patients with different rRT−PCR test results during the first 3 weeks of the outbreak in Qazvin province, Iran. Methods −For this retrospective cohort study, data of hospitalized patients primarily diagnosed as having COVID−19 in all 12 centers across the whole Qazvin province during Feb 20−Mar 11, 2020 was analyzed. A multivariate logistic regression model was applied to assess the independent associates of death among COVID−19 patients. Results − 998 patients (57% male, median age 54 years) with positive chest CT−scan changes were included in this study. Among them, 558 patients were examined with rRT−PCR test and 73.8% tested positive. Case fatality rate was 20.68% and 7.53% among test−positive and test negative hospitalized patients, respectively. While only 5.2% of patients were ICU admitted, case fatality rates outside ICU were 17.70% and 4.65% in test-positive and test-negative non−ICU admitted patients, correspondingly. The independent associates of death were age ≥ 70 years, testing positive with rRT−PCR test, having immunodeficiency disorders and ICU admission. Conclusions − Hospitalized COVID−19 patients with mild symptoms despite positive chest CT changes and major comorbidities were more probable to have negative rRT−PCR test result, hence lower case fatality rate and a more favorable outcome.


title: COVID-19 outbreak in Wuhan demonstrates the limitations of publicly available case numbers for epidemiological modelling.

text: Epidemiological models are widely used to analyse the spread of diseases such as the global COVID-19 pandemic caused by SARS-CoV-2. However, all models are based on simplifying assumptions and on sparse data. This limits the reliability of parameter estimates and predictions. In this manuscript, we demonstrate the relevance of these limitations by performing a study of the COVID-19 outbreak in Wuhan, China. We perform parameter estimation, uncertainty analysis and model selection for a range of established epidemiological models. Amongst others, we employ Markov chain Monte Carlo sampling, parameter and prediction profile calculation algorithms. Our results show that parameter estimates and predictions obtained for several established models on the basis of reported case numbers can be subject to substantial uncertainty. More importantly, estimates were often unrealistic and the confidence / credibility intervals did not cover plausible values of critical parameters obtained using different approaches. These findings suggest, amongst others, that several models are over-simplistic and that the reported case numbers provide often insufficient information.


title: Estimating the number of COVID-19-related infections, deaths and hospitalizations in Iran under different physical distancing and isolation scenarios: A compartmental mathematical modeling

text: Background: Iran is one of the countries that has been overwhelmed with COVID-19. We aimed to estimate the total number of COVID-19 related infections, deaths, and hospitalizations in Iran under different physical distancing and isolation scenarios. Methods: We developed a Susceptible-Exposed-Infected-Removed (SEIR) model, parameterized to the COVID-19 pandemic in Iran. We used the model to quantify the magnitude of the outbreak in Iran and assess the effectiveness of isolation and physical distancing under five different scenarios (A: 0% isolation, through E: 40% isolation of all infected cases). We used Monte-Carlo simulation to calculate the 95% uncertainty intervals (UI). Findings: Under scenario A, we estimated 5,196,000 (UI 1,753,000 - 10,220,000) infections to happen till mid-June with 966,000 (UI 467,800 - 1,702,000) hospitalizations and 111,000 (UI 53,400 - 200,000) deaths. Successful implantation of scenario E would reduce the number of infections by 90% (i.e. 550,000) and change the epidemic peak from 66,000 on June 9th to 9,400 on March 1st. Scenario E also reduces the hospitalizations by 92% (i.e. 74,500), and deaths by 93% (i.e. 7,800). Interpretation: With no approved vaccination or therapy, we found physical distancing and isolation that includes public awareness and case-finding/isolation of 40% of infected people can reduce the burden of COVID-19 in Iran by 90% by mid-June.


title: The invisible workforce during the COVID-19 pandemic: Family carers at the frontline

text: This is an open letter to acknowledge the essential and increasingly challenging role unpaid family carers are playing in the COVID-19 pandemic. The letter is written by members of the CAREWELL team, a HRB-funded project that aims to promote health and self-care behaviours among working family carers. Family carers provide care to family and friends in the community who need support due to old-age, disability and chronic illness. In many cases, family carers are supporting those who are considered most at risk in this pandemic meaning carers must reduce their own risk of infection in order to protect their dependent family members. The temporary reduction of some home care services, as well as school and creche closures, means that family carers are providing increased levels of care with little or no support. At a time when both worlds of work and care have been dramatically transformed, we wish to shed light on those who are currently balancing paid employment with a family caregiving role. We argue that there is much to be learned from the recent work restrictions that could benefit employees, including working family carers, beyond this pandemic. We also wish to build on the potential positives of a transformed society and encourage policy makers and employers to focus on what is currently being implemented, and to identify which measures could be used to create a bedrock of policies and practices that would offer robust and effective support to family carers. It is hoped that family carers will receive greater recognition for the significant role they play in society, providing essential care and alleviating the strain on health and social care systems, both during and post the COVID-19 pandemic.


title: COVID-19: a crash test for biomedical publishing?

text: The effect of COVID-19 on biomedical publishing (BP) (i.e. scientific biomedical periodicals continuously published by research communities or commercial publishers) has not been deeply explored. To estimate the immediate COVID-19 impact on BP, we have assessed PubMed-indexed articles about COVID-19 (PMIAC) from December 2019 to April 2020. PMIAC have been classified according to publication date, country, and journals for evaluation of time-, region- and scientometric-dependant impact of COVID-19 on BP and have been curated manually (i.e. each entry has been individually analyzed). PMIAC analysis reflects geographic and temporal parameters of outbreak spread. A major BP problem is related to the fact that only 40% of articles report/review/analyze data. Another BP weakness is the clusterization of "highly-trusted" publications according to countries of origin and "highly impacting" journals. Finally, a problem highlighted by COVID-19 crisis is the increased specification of biomedical research. To solve the problem, analytical reviews integrating data from different areas of biology and medicine are required. The data on PMIAC suggest priority of "what is published" over "where it is published" and "who are the authors". We believe that our brief analysis may help to shape forthcoming BP to become more effective in solving immediate problems resulted from global threats.


title: Maximum entropy method for estimating the reproduction number: An investigation for COVID-19 in China

text: The key parameter that characterizes the transmissibility of a disease is the reproduction number R. If it exceeds 1, the number of incident cases will inevitably grow over time, and a large epidemic is possible. To prevent the expansion of an epidemic, R must be reduced to a level below 1. To estimate the reproduction number, the probability distribution function of the generation interval of an infectious disease is required to be available; however, this distribution is often unknown. In this letter, given the incomplete information for the generation interval, we propose a maximum entropy method to estimate the reproduction number. Based on this method, given the mean value and variance of the generation interval, we first determine its probability distribution function and in turn estimate the real-time values of reproduction number of COVID-19 in China. By applying these estimated reproduction numbers into the susceptible-infectious-removed epidemic model, we simulate the evolutionary track of the epidemic in China, which is well in accordance with that of the real incident cases. The simulation results predict that China's epidemic will gradually tend to disappear by May 2020 if the quarantine measures can continue to be executed.


title: Oncology during the COVID-19 pandemic: challenges, dilemmas and the psychosocial impact on cancer patients

text: COVID-19 has caused unprecedented societal turmoil, triggering a rapid, still ongoing, transformation of healthcare provision on a global level. In this new landscape, it is highly important to acknowledge the challenges this pandemic poses on the care of the particularly vulnerable cancer patients and the subsequent psychosocial impact on them. We have outlined our clinical experience in managing patients with gastrointestinal, hematological, gynaecological, dermatological, neurological, thyroid, lung and paediatric cancers in the COVID-19 era and have reviewed the emerging literature around barriers to care of oncology patients and how this crisis affects them. Moreover, evolving treatment strategies and novel ways of addressing the needs of oncology patients in the new context of the pandemic are discussed.


title: CT findings of severe novel coronavirus disease (COVID-19): A case report of Heilongjiang Province, China

text: 2019 novel coronavirus disease (COVED-19, previously known as novel coronavirus pneumonia) was first discovered in December 2019 and spread widely in China and all over the world in 2020 The initial symptoms of most patients include fever, cough, and fatigue Dyspnea may occur with the progress of the disease, and acute respiratory distress syndrome may occur in severe cases The CT manifestations of this disease are mainly ground-glass opacity (GGO) in the lung, which may be accompanied by patchy consolidation, and fibrous changes may appear in the lung at the later stage of the disease Combined with typical clinical and imaging findings and positive nucleic acid test results, the disease can be diagnosed We report the first case of novel coronavirus disease (COVED-19) in Heilongjiang Province, China The patient was seriously ill, who felt that he suffered from fever, fatigue, cough, and expectoration and sought medical treatment, with a history of contact with Wuhan The leukocyte count was normal, and the lymphocyte count was decreased CT imaging showed large GGO and partial patchy consolidation in both lungs The patient recovered and was discharged after 26 days of treatment This study is helpful for early diagnosis and timely clinical management by mastering the typical imaging of novel coronavirus disease (COVED-19)


title: Cryo-EM structures reveal transcription initiation steps by yeast mitochondrial RNA polymerase

text: Cryo-EM structures of transcription pre-initiation complex (PIC) and initiation complex (IC) of yeast mitochondrial RNA polymerase show fully resolved transcription bubbles and explain promoter melting, template alignment, DNA scrunching, transition into elongation, and abortive synthesis. Promoter melting initiates in PIC with MTF1 trapping the −4 to −2 non-template (NT) bases in its NT-groove. Transition to IC is marked by a large-scale movement that aligns the template with RNA at the active site. RNA synthesis scrunches the NT strand into an NT-loop, which interacts with centrally positioned MTF1 C-tail. Steric clashes of the C-tail with RNA:DNA and NT-loop, and dynamic scrunching-unscrunching of DNA explain abortive synthesis and transition into elongation. Capturing the catalytically active IC-state with UTPαS poised for incorporation enables modeling toxicity of antiviral nucleosides/nucleotides.


title: Estimating the presymptomatic transmission of COVID19 using incubation period and serial interval data

text: We estimated the fraction and timing of presymptomatic transmissions of COVID19 with mathematical models combining the available data of the incubation period and serial interval. We found that up to 79.7% transmissions could be presymptomatic among the imported cases in China outside Wuhan. The average timing of presymptomatic transmissions is 3.8 days (SD = 6.1) before the symptom onset, which is much earlier than previously assumed.


title: The Time for Universal Masking of the Public for Coronavirus Disease 2019 Is Now

text: In this perspective, we recommend universal masking of the US public during coronavirus disease 2019 due to the high contagiousness of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), viral shedding of viable SARS-CoV-2 from asymptomatic individuals, and the likely contribution of masking to core distancing public health strategies for curbing transmission.


title: Drug, chemical firms open COVID-19 patents

text: Gilead Sciences has signed royalty-free license agreements allowing five generic drug firms to make and distribute its antiviral drug remdesivir in 127 countries The targeted countries are low income or “face significant obstacles to healthcare access,” Gilead says Supplies of the drug are severely limited;as of January, Gilead was not regularly making it The US gave emergency approval for remdesivir to treat COVID-19 at the end of April The firm has since been ramping up output, with the goal of supplying 1 million treatment courses by the end of 2020 Gilead describes remdesivir production as “a long, linear chemical synthesis process that must be completed sequentially and includes several specialized chemistry steps and novel substances with limited global availability ” The arrangement—with Cipla, Ferozsons Laboratories, Hetero, Jubilant Life Sciences, and Mylan—should increase global supply of remdesivir, Gilead says In addition to rights to the drug, Gilead will share its manufacturing,,,,


title: CHEER: hierarCHical taxonomic classification for viral mEtagEnomic data via deep leaRning

text: The fast accumulation of viral metagenomic data has contributed significantly to new RNA virus discovery. However, the short read size, complex composition, and large data size can all make taxonomic analysis difficult. In particular, commonly used alignment-based methods are not ideal choices for detecting new viral species. In this work, we present a novel hierarchical classification model named CHEER, which can conduct read-level taxonomic classification from order to genus for new species. By combining k-mer embedding-based encoding, hierarchically organized CNNs, and carefully trained rejection layer, CHEER is able to assign correct taxonomic labels for reads from new species. We tested CHEER on both simulated and real sequencing data. The results show that CHEER can achieve higher accuracy than popular alignment-based and alignment-free taxonomic assignment tools. The source code, scripts, and pre-trained parameters for CHEER are available via GitHub: https://github.com/KennthShang/CHEER.


title: Epidemiological parameters of coronavirus disease 2019: a pooled analysis of publicly reported individual data of 1155 cases from seven countries

text: Background The outbreak of coronavirus disease 2019 (COVID-19) has been declared a pandemic by the World Health Organization, while several key epidemiological parameters of the disease remain to be clarified. This study aimed to obtain robust estimates of the incubation period, upper limit of latent period (interval between exposure of infector and infectee), serial interval, time point of exposure and basic reproduction number (R0) of COVID-19. Methods Between late February and early March of 2020, the individual data of laboratory confirmed cases of COVID-19 were retrieved from 10728 publicly available reports released by the health authorities of and outside China and from 1790 publications identified in PubMed and CNKI. To be eligible, a report had to contain the data that allowed for estimation of at least one parameter. As relevant data mainly came from clustering cases, the clusters for which no evidence was available to establish transmission order were all excluded to ensure accuracy of estimates. Additionally, only the cases with an exposure period spanning 3 days or less were included in the estimation of parameters involving exposure date, and a simple method for determining exposure date was adopted to ensure the error of estimates be small (< 0.3 day). Depending on specific parameters, three or four of normal, lognormal, Weibull, and gamma distributions were fitted to the datasets and the results from appropriate models were presented. Findings In total, 1155 cases from China, Japan, Singapore, South Korea, Vietnam, Germany and Malaysia were included for the final analysis. The mean and standard deviation were 7.44 days and 4.39 days for incubation period, 2.52 days and 3.95 days for the upper limit of latent period, 6.70 days and 5.20 days for serial interval, and -0.19 day (i.e., 0.19 day before symptom onset of infector) and 3.32 days for time point of exposure. R0 was estimated to be 1.70 and 1.78 based on two different formulas. For 39 (6.64%) cases, the incubation periods were longer than 14 days. In 102 (43.78%) infector-infectee pairs, transmission occurred before the symptom onsets of infectors. In 27 (3.92%) infector-infectee pairs, symptom onsets of infectees occurred before those of infectors. Stratified analysis showed that incubation period and serial interval were consistently longer for those with less severe disease and for those whose primary cases had less severe disease. Asymptomatic transmission was also observed. Interpretation This study obtained robust estimates of several key epidemiological parameters of COVID-19. The findings support current practice of 14-day quarantine of persons with potential exposure, but also suggest that longer monitoring periods might be needed for selected groups. The estimates of serial interval, time point of exposure and latent period provide consistent evidence on pre-symptomatic transmission. This together with asymptomatic transmission and the generally longer incubation and serial interval of less severe cases suggests a high risk of long-term epidemic in the absence of appropriate control measures.


title: Evaluation of Different PCR Assay Formats for Sensitive and Specific Detection of SARS-CoV-2 RNA

text: Accurate identification of individuals infected with SARS-CoV-2 is crucial for efforts to control the ongoing COVID-19 pandemic. Polymerase chain reaction (PCR)-based assays are the gold standard for detecting viral RNA in patient samples and are used extensively in clinical settings. Most currently used quantitative PCR (RT-qPCRs) rely upon real-time detection of PCR product using specialized laboratory equipment. To enable the application of PCR in resource-poor or non-specialist laboratories, we have developed and evaluated a nested PCR method for SARS-CoV-2 RNA using simple agarose gel electrophoresis for product detection. Using clinical samples tested by conventional qPCR methods and RNA transcripts of defined RNA copy number, the nested PCR based on the RdRP gene demonstrated high sensitivity and specificity for SARS-CoV-2 RNA detection in clinical samples, but showed variable and transcript length-dependent sensitivity for RNA transcripts. Samples and transcripts were further evaluated in an additional N protein real-time quantitative PCR assay. As determined by 50% endpoint detection, the sensitivities of three RT-qPCRs and nested PCR methods varied substantially depending on the transcript target with no method approaching single copy detection. Overall, these findings highlight the need for assay validation and optimization and demonstrate the inability to precisely compare viral quantification from different PCR methodologies without calibration.


docid: lgmdpxcl

title: Cumulative incidence and diagnosis of SARS-CoV-2 infection in New York

text: Importance: New York State (NYS) is an epicenter of the United States' COVID-19 epidemic. Reliable estimates of cumulative incidence of SARS-CoV-2 infection in the population are critical to tracking the extent of transmission and informing policies, but US data are lacking, in part because societal closure complicates study conduct. Objective: To estimate the cumulative incidence of SARS-CoV-2 infection and percent of infections diagnosed in New York State, overall and by region, age, sex, and race and ethnicity. Design: Statewide cross-sectional seroprevalence study, conducted April 19-28, 2020. Setting: Grocery stores (n=99) located in 26 counties throughout NYS, which were essential businesses that remained open during a period of societal closure and attract a heterogenous clientele. Participants: Convenience sample of patrons >=18 years and residing in New York State, recruited consecutively upon entering stores and via an in-store flyer. Exposures: Region (New York City, Westchester/Rockland, Long Island, Rest of New York State), age, sex, race and ethnicity. Main Outcomes: Primary outcome: cumulative incidence of SARS-CoV-2 infection, based on dry-blood spot (DBS) SARS-CoV-2 antibody reactivity; secondary outcome: percent of infections diagnosed. Results: Among 15,101 adults with suitable DBS specimens, 1,887 (12.5%) were reactive using a validated SARS-CoV-2 IgG microsphere immunoassay (sensitivity 87.9%, specificity 99.75%). Following post-stratification weighting on region, sex, age, and race and ethnicity and adjustment for assay characteristics, estimated cumulative incidence through March 29 was 14.0% (95% CI: 13.3-14.7%), corresponding to 2,139,300 (95% CI: 2,035,800-2,242,800) infection-experienced adults. Cumulative incidence was higher among Hispanic/Latino (29.2%, 95% CI: 27.2-31.2%), non-Hispanic black/African American (20.2% 95% CI, 18.1-22.3%), and non-Hispanic Asian (12.4%, 95% CI: 9.4-15.4%) adults than non-Hispanic white adults (8.1%, 95% CI: 7.4-8.7%, p<.0001). Cumulative incidence was highest in New York City (NYC) 22.7% (95% CI: 21.5%-24.0). Dividing diagnoses reported to NYS by estimated infection-experienced adults, an estimated 8.9% (95% CI: 8.4-9.3%) of infections were diagnosed, with those [≥]55 years most likely to be diagnosed (11.3%, 95% CI: 10.4-12.2%). Conclusions and Relevance: Over 2 million adults were infected through late March 2020, with substantial variations by subpopulations. As this remains below herd immunity thresholds, monitoring, testing, and contact tracing remain essential public health strategies.


title: Coronavirus and anesthesia/ Coronavirus y anestesia

text: The pandemic of the new coronavirus disease, COVID-19 has been involved in more than 800,000 cases worldwide. There isn’t vaccine or specific treatment. As specialists in airway management, anesthesiologist are routinely exposed to patients’ respiratory secretions and are at high risk of contracting COVID-19 from infected patients. This review provides suggestions on how to minimize this risk by improved infection control.


docid: tnoybbfx

title: Real-time biomedical knowledge synthesis of the exponentially growing world wide web using unsupervised neural networks

text: Decoding disease mechanisms for addressing unmet clinical need demands the rapid assimilation of the exponentially growing biomedical knowledge. These are either inherently unstructured and non-conducive to current computing paradigms or siloed into structured databases requiring specialized bioinformatics. Despite the recent renaissance in unsupervised neural networks for deciphering unstructured natural languages and the availability of numerous bioinformatics resources, a holistic platform for real-time synthesis of the scientific literature and seamless triangulation with deep omic insights and real-world evidence has not been advanced. Here, we introduce the nferX platform that makes the highly unstructured biomedical knowledge computable and supports the seamless visual triangulation with statistical inference from diverse structured databases. The nferX platform will accelerate and amplify the research potential of subject-matter experts as well as non-experts across the life science ecosystem (https://academia.nferx.com/).


title: Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic

text: There are outstanding evolutionary questions on the recent emergence of coronavirus SARS-CoV-2/hCoV-19 in Hubei province that caused the COVID-19 pandemic, including (1) the relationship of the new virus to the SARS-related coronaviruses, (2) the role of bats as a reservoir species, (3) the potential role of other mammals in the emergence event, and (4) the role of recombination in viral emergence. Here, we address these questions and find that the sarbecoviruses – the viral subgenus responsible for the emergence of SARS-CoV and SARS-CoV-2 – exhibit frequent recombination, but the SARS-CoV-2 lineage itself is not a recombinant of any viruses detected to date. In order to employ phylogenetic methods to date the divergence events between SARS-CoV-2 and the bat sarbecovirus reservoir, recombinant regions of a 68-genome sarbecovirus alignment were removed with three independent methods. Bayesian evolutionary rate and divergence date estimates were consistent for all three recombination-free alignments and robust to two different prior specifications based on HCoV-OC43 and MERS-CoV evolutionary rates. Divergence dates between SARS-CoV-2 and the bat sarbecovirus reservoir were estimated as 1948 (95% HPD: 1879-1999), 1969 (95% HPD: 1930-2000), and 1982 (95% HPD: 1948-2009). Despite intensified characterization of sarbecoviruses since SARS, the lineage giving rise to SARS-CoV-2 has been circulating unnoticed for decades in bats and been transmitted to other hosts such as pangolins. The occurrence of a third significant coronavirus emergence in 17 years together with the high prevalence and virus diversity in bats implies that these viruses are likely to cross species boundaries again. In Brief The Betacoronavirus SARS-CoV-2 is a member of the sarbecovirus subgenus which shows frequent recombination in its evolutionary history. We characterize the extent of this genetic exchange and identify non-recombining regions of the sarbecovirus genome using three independent methods to remove the effects of recombination. Using these non-recombining genome regions and prior information on coronavirus evolutionary rates, we obtain estimates from three approaches that the most likely divergence date of SARS-CoV-2 from its most closely related available bat sequences ranges from 1948 to 1982. Key Points RaTG13 is the closest available bat virus to SARS-CoV-2; a sub-lineage of these bat viruses is able to infect humans. Two sister lineages of the RaTG13/SARS-CoV-2 lineage infect Malayan pangolins. The sarbecoviruses show a pattern of deep recombination events, indicating that there are high levels of co-infection in horseshoe bats and that the viral pool can generate novel allele combinations and substantial genetic diversity; the sarbecoviruses are efficient ‘explorers’ of phenotype space. The SARS-CoV-2 lineage is not a recent recombinant, at least not involving any of the bat or pangolin viruses sampled to date. Non-recombinant regions of the sarbecoviruses can be identified, allowing for phylogenetic inference and dating to be performed. We constructed three such regions using different methods. We estimate that RaTG13 and SARS-CoV-2 diverged 40 to 70 years ago. There is a diverse unsampled reservoir of generalist viruses established in horseshoe bats. While an intermediate host responsible for the zoonotic event cannot be ruled out, the relevant evolution for spillover to humans very likely occurred in horseshoe bats.


title: Covid-19 predictions using a Gauss model, based on data from April 2

text: We propose a Gauss model (GM), a map from time to the bell-shaped Gauss function to model the casualties per day and country, as a quick and simple model to make predictions on the coronavirus epidemic. Justified by the sigmoidal nature of a pandemic, i.e. initial exponential spread to eventual saturation, we apply the GM to the first corona pandemic wave using data from 25 countries, for which a sufficient amount of not yet fully developed data exists, as of April 2, 2020, and study the model's predictions. We find that logarithmic daily fatalities caused by Covid-19 are well described by a quadratic function in time. By fitting the data to second order polynomials from a statistical chi2-fit with 95% confidence, we are able to obtain the characteristic parameters of the GM, i.e. a width, peak height and time of peak, for each country separately. We provide evidence that this supposedly oversimplifying model might still have predictive power and use it to forecast the further course of the fatalities caused by Covid-19 per country, including peak number of deaths per day, date of peak, and duration within most deaths occur. While our main goal is to present the general idea of the simple modeling process using GMs, we also describe possible estimates for the number of required respiratory machines and the duration left until the number of infected will be significantly reduced.


title: A Fast and Accessible Method for the Isolation of RNA, DNA, and Protein to Facilitate the Detection of SARS-CoV-2

text: Management of the COVID-19 pandemic requires widespread SARS-CoV-2 testing. A main limitation for widespread SARS-CoV-2 testing is the global shortage of essential supplies, among these, RNA extraction kits. The need for commercial RNA extraction kits places a bottleneck on tests that detect SARS-CoV-2 genetic material, including PCR-based reference tests. Here we propose an alternative method we call PEARL (Precipitation Enhanced Analyte RetrievaL) that addresses this limitation. PEARL uses a lysis solution that disrupts cell membranes and viral envelopes while simultaneously providing conditions suitable for alcohol-based precipitation of RNA, DNA, and proteins. PEARL is a fast, low-cost, and simple method that uses common laboratory reagents and offers comparable performance to commercial RNA extraction kits. PEARL offers an alternative method to isolate host and pathogen nucleic acids and proteins to streamline the detection of DNA and RNA viruses, including SARS-CoV-2.


title: Global genetic patterns reveal host tropism versus cross-taxon transmission of bat Betacoronaviruses

text: Emerging infectious diseases due to coronavirus (CoV) infections have received significant global attention in the past decade and have been linked to bats as the original source. The diversity, distribution, and host associations of bat CoVs were investigated to assess their potential for zoonotic transmission. Phylogenetic, network, and principal coordinate analysis confirmed the classification of betacoronaviruses (BetaCoVs) into five groups (2A to 2E) and a potentially novel group, with further division of 2D into five subgroups. The genetic co-clustering of BetaCoVs among closely related bats reflects host taxon-specificity with each bat family as the host for a specific BetaCoV group, potentially a natural barrier against random transmission. The divergent pathway of BetaCoV and host evolution suggests that the viruses were introduced just prior to bat dispersal and speciation. As such, deviant patterns were observed such as for 2D-IV, wherein cross-taxon transmission due to overlap in bat habitats and geographic range among genetically divergent African bat hosts could have played a strong role on their shared CoV lineages. In fact, a few bat taxa especially the subfamily Pteropodinae were shown to host diverse groups of BetaCoVs. Therefore, ecological imbalances that disturb bat distribution may lead to loss of host specificity through cross-taxon transmission and multi-CoV infection. Hence, initiatives that minimize the destruction of wildlife habitats and limit wildlife-livestock-human interfaces are encouraged to help maintain the natural state of bat BetaCoVs in the wild. Importance Bat Betacoronaviruses (BetaCoVs) pose a significant threat to global public health and have been implicated in several epidemics such as the recent pandemic by severe acute respiratory syndrome coronavirus 2. Here, we show that bat BetaCoVs are predominantly host-specific, which could be a natural barrier against infection of other host types. However, a strong overlap in bat habitat and geographic range may facilitate viral transmission to unrelated hosts, and a few bat families have already been shown to host multi-CoV variants. We predict that continued disturbances on the ecological balance may eventually lead to loss of host specificity. When combined with enhanced wildlife-livestock-human interfaces, spillover to humans may be further facilitated. We should therefore start to define the ecological mechanisms surrounding zoonotic events. Global surveillance should be expanded and strengthened to assess the complete picture of bat coronavirus diversity and distribution and their potential to cause spillover infections.


title: Computational methods to develop potential neutralizing antibody Fab region against SARS-CoV-2 as therapeutic and diagnostic tool

text: SARS-CoV-2, a global pandemic originated from Wuhan city of China in the month of December 2019. There is an urgency to identify potential antibodies to neutralize the virus and also as a diagnostic tool candidate. At present palliative treatments using existing antiviral drugs are under trails to treat SARS-CoV-2.Whole Genome sequence of Wuhan market sample of SARS-CoV-2 was obtained from NCBI Gene ID MN908947.3.Spike protein sequence PDB ID 6VSB obtained from RCSB database. Spike protein sequence had shown top V gene match with IGLV1-44*01, IGLV1-47*02 and has VL type chain. Whole Genome sequence had shown top V gene match with IGHV1-38-4*01 and has VH type chain. VD chain had shown link to allele HLA-A0206 80%, HLA-A0217 80%, HLA-A2301 75%, HLA-A0203 75%, HLA-A0202 70% and HLA-A0201 55% of binding levels. Some conserved regions of spike protein had shown strong binding affinity with HLA-A-0*201, HLA-A24, HLA-B-5701 and HLA-B-5703 alpha chains. Synthetic Fab construct BCR type antibody IgG (CR5840) had shown Polyspecific binding activity with spike glycoprotein when compared with available Anti-SARS antibody CR3022.Thus we propose CR5840 Fab constructed antibody as potential neutralizing antibody for SARS-CoV-2. Based on germline analysis we also propose cytotoxic T lymphocyte epitope peptide selective system as effective tool for the development of SARS-CoV-2 vaccine.


title: Evaluation of Nucleocapsid and Spike Protein-based ELISAs for detecting antibodies against SARS-CoV-2

text: Background: At present, PCR-based nucleic acid detection cannot meet the demands for coronavirus infectious disease (COVID-19) diagnosis. Methods: 214 confirmed COVID-19 patients who were hospitalized in the General Hospital of Central Theater Command of the People's Liberation Army between January 18 and February 26, 2020, were recruited. Two Enzyme-Linked Immunosorbent Assay (ELISA) kits based on recombinant SARS-CoV-2 nucleocapsid protein (rN) and spike protein (rS) were used for detecting IgM and IgG antibodies, and their diagnostic feasibility was evaluated. Results: Among the 214 patients, 146 (68.2%) and 150 (70.1%) were successfully diagnosed with the rN-based IgM and IgG ELISAs, respectively; 165 (77.1%) and 159 (74.3%) were successfully diagnosed with the rS-based IgM and IgG ELISAs, respectively. The positive rates of the rN-based and rS-based ELISAs for antibody (IgM and/or IgG) detection were 80.4% and 82.2%, respectively. The sensitivity of the rS-based ELISA for IgM detection was significantly higher than that of the rN-based ELISA. We observed an increase in the positive rate for IgM and IgG with an increasing number of days post-disease onset (d.p.o.), but the positive rate of IgM dropped after 35 d.p.o. The positive rate of rN-based and rS-based IgM and IgG ELISAs was less than 60% during the early stage of the illness 0-10 d.p.o., and that of IgM and IgG was obviously increased after 10 d.p.o. Conclusions: ELISA has a high sensitivity, especially for the detection of serum samples from patients after 10 d.p.o, it can be an important supplementary method for COVID-19 diagnosis.


title: A putative new SARS-CoV protein, 3a*, encoded in an ORF overlapping ORF3a

text: Identification of the full complement of genes in SARS-CoV-2 is a crucial step towards gaining a fuller understanding of its molecular biology. However, short and/or overlapping genes can be difficult to detect using conventional computational approaches, whereas high throughput experimental approaches – such as ribosome profiling – cannot distinguish translation of functional peptides from regulatory translation or translational noise. By studying regions showing enhanced conservation at synonymous sites in alignments of SARS-CoV and related viruses (subgenus Sarbecovirus), and correlating with the conserved presence of an open reading frame and plausible translation mechanism, we identified a putative new gene, ORF3a*, overlapping ORF3a in an alternative reading frame. A recently published ribosome profiling study confirmed that ORF3a* is indeed translated during infection. ORF3a* is conserved across the subgenus Sarbecovirus, and encodes a 40–41 amino acid predicted transmembrane protein.


title: Impact on mental health care and on mental health service users of the COVID-19 pandemic: a mixed methods survey of UK mental health care staff

text: Purpose: The COVID-19 pandemic has potential to disrupt and burden the mental health care system, and to magnify inequalities experienced by mental health service users. Methods: We investigated staff reports regarding the impact of the COVID-19 pandemic in its early weeks on mental health care and mental health service users in the UK using a mixed methods online survey. Recruitment channels included professional associations and networks, charities and social media. Quantitative findings were reported with descriptive statistics, and content analysis conducted for qualitative data. Results: 2,180 staff from a range of sectors, professions and specialties participated. Immediate infection control concerns were highly salient for inpatient staff, new ways of working for community staff. Multiple rapid adaptations and innovations in response to the crisis were described, especially remote working. This was cautiously welcomed but found successful in only some clinical situations. Staff had specific concerns about many groups of service users, including people whose conditions are exacerbated by pandemic anxieties and social disruptions; people experiencing loneliness, domestic abuse and family conflict; those unable to understand and follow social distancing requirements; and those who cannot engage with remote care. Conclusion: This overview of staff concerns and experiences in the early COVID-19 pandemic suggests directions for further research and service development: we suggest that how to combine infection control and a therapeutic environment in hospital, and how to achieve effective and targeted tele-health implementation in the community, should be priorities. The limitations of our convenience sample must be noted.


title: The potential impact of the COVID-19 pandemic on tuberculosis: a modelling analysis

text: Background Routine services for tuberculosis (TB) are being disrupted by stringent lockdowns against the novel SARS-CoV-2 virus. We sought to estimate the potential long-term epidemiological impact of such disruptions on TB burden in high-burden countries, and how this negative impact could be mitigated. Methods We adapted mathematical models of TB transmission in three high-burden countries (India, Kenya and Ukraine) to incorporate lockdown-associated disruptions in the TB care cascade. The anticipated level of disruption reflected consensus from a rapid expert consultation. We modelled the impact of these disruptions on TB incidence and mortality over the next five years, and also considered potential interventions to curtail this impact. Results Even temporary disruptions can cause long-term increases in TB incidence and mortality. We estimated that a 3-month lockdown, followed by 10 months to restore normal TB services, would cause, over the next 5 years, an additional 1.92 million TB cases (Crl 1.74 - 2.15) and 488,000 TB deaths (CrI 449 - 541 thousand) in India, 48,000 (33,400 - 72,320) TB cases and 16,800 deaths (11.9 - 21.9 thousand) in Kenya, and 9,100 (6,980 - 11,200) cases and 1,960 deaths (1,620 - 2,350) in Ukraine. However, any such negative impacts could be averted through supplementary 'catch-up' TB case detection and treatment, once restrictions are eased. Interpretation Lockdown-related disruptions can cause long-lasting increases in TB burden, but these negative effects can be mitigated with targeted interventions implemented rapidly once lockdowns are lifted.


docid: qqnhptlc

title: Who is an expert on the COVID-19 crisis?


title: Unexpected free fatty acid binding pocket in the cryo-EM structure of SARS-CoV-2 spike protein

text: COVID-19, caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), represents a global crisis. Key to SARS-CoV-2 therapeutic development is unraveling the mechanisms driving high infectivity, broad tissue tropism and severe pathology. Our cryo-EM structure of SARS-CoV-2 spike (S) glycoprotein reveals that the receptor binding domains (RBDs) tightly and specifically bind the essential free fatty acid (FFA) linoleic acid (LA) in three composite binding pockets. The pocket also appears to be present in the highly pathogenic coronaviruses SARS-CoV and MERS-CoV. Lipid metabolome remodeling is a key feature of coronavirus infection, with LA at its core. LA metabolic pathways are central to inflammation, immune modulation and membrane fluidity. Our structure directly links LA and S, setting the stage for interventions targeting LA binding and metabolic remodeling by SARS-CoV-2. One Sentence Summary A direct structural link between SARS-CoV-2 spike and linoleic acid, a key molecule in inflammation, immune modulation and membrane fluidity.


title: Assessment of metagenomic sequencing and qPCR for detection of influenza D virus in bovine respiratory tract samples

text: High throughput sequencing is currently revolutionizing the genomics field and providing new approaches to the detection and characterization of microorganisms. The objective of this study was to assess the detection of influenza D virus (IDV) in bovine respiratory tract samples using two sequencing platforms (MiSeq and Nanopore (GridION)), and species-specific qPCR. An IDV-specific qPCR was performed on 232 samples (116 nasal swabs and 116 tracheal washes) that had been previously subject to virome sequencing using MiSeq. Nanopore sequencing was performed on 19 samples positive for IDV by either MiSeq or qPCR. Nanopore sequence data was analyzed by two bioinformatics methods: What’s In My Pot (WIMP, on the EPI2ME platform), and an in-house developed analysis pipeline. The agreement of IDV detection between qPCR and MiSeq was 82.3%, between qPCR and Nanopore was 57.9% (in-house) and 84.2% (WIMP), and between MiSeq and Nanopore was 89.5% (in-house) and 73.7% (WIMP). IDV was detected by MiSeq in 14 of 17 IDV qPCR-positive samples with Cq (cycle quantification) values below 31, despite multiplexing 50 samples for sequencing. When qPCR was regarded as the gold standard, the sensitivity and specificity of MiSeq sequence detection were 28.3% and 98.9%, respectively. We conclude that both MiSeq and Nanopore sequencing are capable of detecting IDV in clinical specimens with a range of Cq values. Sensitivity may be further improved by optimizing sequence data analysis, improving virus enrichment, or reducing the degree of multiplexing.


title: Clinical And Analytical Performance Of An Automated Serological Test That Identifies S1/S2 Neutralizing IgG In Covid-19 Patients Semiquantitatively

text: BACKGROUND In the Covid-19 pandemic, highly selective serological testing is essential to define exposure to SARS-CoV-2 virus. Many tests have been developed, yet with variable speed to first result, and of unknown quality, particularly when considering the prediction of neutralizing capacity. OBJECTIVES/METHODS The LIAISON® SARS-CoV-2 S1/S2 IgG assay was designed to measure antibodies against the SARS-CoV-2 native S1/S2 proteins in a standardized automated chemiluminescent assay. Clinical and analytical performance of the test were validated in an observational study using residual samples (>1500) with positive or negative Covid-19 diagnosis. RESULTS The LIAISON® SARS-CoV-2 S1/S2 IgG assay proved highly selective and specific, and offers semiquantitative measures of serum or plasma levels of anti-S1/S2 IgG with neutralizing activity. The diagnostic sensitivity was 91.3% and 95.7% at >5 or ≥15 days from diagnosis respectively, and 100% when assessed against a neutralizing assay. The specificity ranged between 97% and 98.5%. The average imprecision of the assay was <5 % coefficient of variation. Assay performance at 2 different cut-offs was evaluated to optimize predictive values in settings with different % disease prevalence. CONCLUSIONS. The automated LIAISON® SARS-CoV-2 S1/S2 IgG assay brings efficient, sensitive, specific, and precise serological testing to the laboratory, with the capacity to test large amounts of samples per day: first results are available within 35 minutes with a throughput of 170 tests/hour. The test also provides a semiquantitative measure to identify samples with neutralizing antibodies, useful also for a large scale screening of convalescent plasma for safe therapeutic use. IMPORTANCE With the worldwide advance of the COVID-19 pandemic, efficient, reliable and accessible diagnostic tools are needed to support public health officials and healthcare providers in their efforts to deliver optimal medical care, and articulate sound demographic policy. DiaSorin has developed an automated serology based assay for the measurement of IgG specific to SARS CoV-2 Spike protein, and tested its clinical performance in collaboration with Italian health care professionals who provided access to large numbers of samples from infected and non-infected individuals. The assay delivers excellent sensitivity and specificity, and is able to identify samples with high levels of neutralizing antibodies. This will provide guidance in assessing the true immune status of subjects, as well as meeting the pressing need to screen donors for high titer convalescent sera for subsequent therapeutic and prophylactic use.


title: Assessment of Early Mitigation Measures Against COVID-19 in Puerto Rico: March 15-May 15, 2020

text: Background: On March 15, 2020 Puerto Rico implemented non-pharmaceutical interventions (NPIs), including a mandatory curfew, as part of a state of emergency declaration to mitigate the community transmission of the SARS-CoV-2 virus. The strict enforcement of this curfew was extended through May 25, with a gradual relaxation beginning on May 1. This report summarizes an assessment of these early mitigation measures on the progression of COVID-19 in the island. Methods and Findings: From March 15 to May 15, 2020, 41,748 results of molecular (RT-PCR) tests were reported to the Puerto Rico Department of Health. Of these, 1,866 (4.5%) were positive, corresponding to 1,219 individuals with COVID-19 included in the study. We derived the epidemic growth rates (r) and the corresponding reproductive numbers (R) from the epidemic curve of these 1,219 individuals with laboratory-confirmed diagnosis of COVID-19 using their date of test collection as a proxy for symptoms onset. We then compared the observed cases with the R-based epidemic model projections had the mitigation measures not been implemented. Computations were conducted in the R packages forecast, incidence and projections. The number of daily RT-PCR-confirmed cases peaked on March 30 (84 cases), showing a weekly cyclical trend, with lower counts on weekends and a decreasing secular trend since March 30. The initial exponential growth rate (r) was 17.0% (95% CI: 8.4%, 25.6%), corresponding to a doubling of cases every 4.1 days, and to a reproduction number (Ro) of 1.89 (95% CI: 1.41, 2.39). After March 30, the r value reverted to an exponential decay rate (negative) of -3.6% (95% CI: -5.7%, -1.4%), corresponding to a halving of cases every 19.4 days and to an Ro of 0.90 (95% CI: 0.84, 0.97). Had the initial growth rate been maintained, a total of 18,699 (96%CI: 4,113, 87,438) COVID-19 cases would have occurred by April 30 compared with 1,119 observed. Conclusions: Our findings are consistent with very effective implementation of early non-pharmaceutical interventions (NPIs) as mitigation measures in Puerto Rico. These results serve as a baseline to assess the impact of the transition from mitigation to containment stages in Puerto Rico.


The International Health Regulations, COVID-19, and bordering practices: Who gets in, what gets out, and who gets rescued?


title: Reduction of cutting forces by elliptical vibration in multi-pass ultraprecise single point axial cutting of V-grooves

text: Abstract Elliptical vibration cutting (EVC) is an advanced micromachining technology that has a wide range of applications in high-precision micro/nano manufacturing. This technology is primarily used in fabrication of micro/nano-scale functional surfaces, geometrical features, optical and holographic components that are cut in ferrous and difficult-to-cut tooling materials with high form accuracy and surface quality. The main objective of this study was to demonstrate the positive effect of EVC motions on cutting force reduction and stabilization. For this purpose, a series of cutting trials involving the fabrication of micro V-grooves by means of the ultraprecise single point cutting (USPC) were performed. To maintain a constant level of the cutting force, an axial multi-pass cutting strategy with constant cutting area was employed. The influence and advantages brought by EVC over the conventional ‘no-EVC’ USPC scenario were initially assessed by means of the theoretical considerations of the cutting force. Following that, experimental generation of V-grooves has demonstrated that the integration of EVC kinematics with USPC motions has the ability to reduce the ‘no-EVC’ cutting forces by more than 90%, to values around 0.1 N for the main axial component. The addition of EVC motions caused a minimal decrease in surface quality whose areal roughness increased from 14 nm in the ‘no-EVC’ case to 16 nm in the ‘with-EVC’ scenario. These observations are expected to open new opportunities in micromachining of micro/nano products, systems, sensors, functional surfaces, and lighting and holographic optics.


title: An exploration of the SARS-CoV-2 spike receptor binding domain (RBD) – a complex palette of evolutionary and structural features

text: SARS-CoV-2 spike protein (S) is associated with the entry of virus inside the host cell by recruiting its loop dominant receptor binding domain (RBD) and interacting with the host ACE2 receptor. Our study deploying a two-tier approach encompassing evolutionary and structural analysis provides a comprehensive picture of the RBD, which could be of potential use for better understanding the RBD and address its druggability issues. Resorting to an ensemble of sequence space exploratory tools including co-evolutionary analysis and deep mutational scans we provide a quantitative insight into the evolutionarily constrained subspace of the RBD sequence space. Guided by structure network analysis and Monte Carlo simulation we highlight regions inside the RBD, which are critical for providing structural integrity and conformational flexibility of the binding cleft. We further deployed fuzzy C-means clustering by plugging the evolutionary and structural features of discrete structure blocks of RBD to understand which structure blocks share maximum overlap based on their evolutionary and structural features. Deploying this multi-tier interlinked approach, which essentially distilled the evolutionary and structural features of RBD, we highlight discrete region, which could be a potential druggable pocket thereby destabilizing the structure and addressing evolutionary routes.