title: Critical role of type III interferon in controlling SARS-CoV-2 infection, replication and spread in primary human intestinal epithelial cells

text: SARS-CoV-2 is an unprecedented worldwide health problem that requires concerted and global approaches to better understand the virus in order to develop novel therapeutic approaches to stop the COVID-19 pandemic and to better prepare against potential future emergence of novel pandemic viruses. Although SARS-CoV-2 primarily targets cells of the lung epithelium causing respiratory infection and pathologies, there is growing evidence that the intestinal epithelium is also infected. However, the importance of the enteric phase of SARS-CoV-2 for virus-induced pathologies, spreading and prognosis remains unknown. Here, using both colon-derived cell lines and primary non-transformed colon organoids, we engage in the first comprehensive analysis of SARS-CoV-2 lifecycle in human intestinal epithelial cells. Our results demonstrate that human intestinal epithelial cells fully support SARS-CoV-2 infection, replication and production of infectious de-novo virus particles. Importantly, we identified intestinal epithelial cells as the best culture model to propagate SARS-CoV-2. We found that viral infection elicited an extremely robust intrinsic immune response where, interestingly, type III interferon mediated response was significantly more efficient at controlling SARS-CoV-2 replication and spread compared to type I interferon. Taken together, our data demonstrate that human intestinal epithelial cells are a productive site of SARS-CoV-2 replication and suggest that the enteric phase of SARS-CoV-2 may participate in the pathologies observed in COVID-19 patients by contributing in increasing patient viremia and by fueling an exacerbated cytokine response.


title: Levenson, former rehab CEO, on his conversion to harm reduction

text: Many people familiar with the addiction treatment field over the past few decades might be surprised to hear that Ben Levenson, the founder of 12-Step-based Origins Behavioral Healthcare in 2009, is no longer a believer in abstinence-based treatment for everyone


title: Antibody assays against SARS-CoV-2: Why a good test does not always produce proper results/ Antikörpertests gegen SARS-CoV-2: Warum ein guter test nicht immer gute ergebnisse produziert

text: Assays to test for antibodies against SARS-CoV-2 can display a high proportion of false-positive results if the frequency of the disease in the general population is low. Testing is not suitable for proving or ruling out an acute infection. Judging an individual patient, a positive antibody titer does not necessarily mean that this person is immune. Currently ELISA assays are not appropriate for individual screening purposes but possibly can complement diagnostic procedures. They are suitable for population-based screening in the context of studies.


title: Screening of healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19 transmission

text: Significant differences exist in the availability of healthcare worker (HCW) SARS-CoV-2 testing between countries, and existing programmes focus on screening symptomatic rather than asymptomatic staff. Over a 3-week period (April 2020), 1,032 asymptomatic HCWs were screened for SARS-CoV-2 in a large UK teaching hospital. Symptomatic staff and symptomatic household contacts were additionally tested. Real-time RT-PCR was used to detect viral RNA from a throat+nose self-swab. 3% of HCWs in the asymptomatic screening group tested positive for SARS-CoV-2. 17/30 (57%) were truly asymptomatic/pauci-symptomatic. 12/30 (40%) had experienced symptoms compatible with coronavirus disease 2019 (COVID-19) >7 days prior to testing, most self-isolating, returning well. Clusters of HCW infection were discovered on two independent wards. Viral genome sequencing showed that the majority of HCWs had the dominant lineage B{middle dot}1. Our data demonstrates the utility of comprehensive screening of HCWs with minimal or no symptoms. This approach will be critical for protecting patients and hospital staff.


title: Longitudinal Saliva Omics Responses to Immune Perturbation: A Case Study

text: Saliva omics, a rapidly developing field for non-invasive diagnostics, may be utilized for monitoring very young or elderly populations, as well as individuals in remote locations. In this study, multiple saliva omics from an individual were monitored over 100 timepoints, over three periods involving: (i) hourly sampling over 24 hours without intervention, (ii) hourly sampling over 24 hours including immune system activation using the standard 23-valent pneumococcal polysaccharide vaccine, (iii) daily sampling for 33 days profiling the post-vaccination response. At each timepoint total saliva transcriptome and proteome were profiled, and salivary extracellular vesicles were derived, from which small-RNA sequencing was used to determine RNA, miRNA, piRNA and bacterial RNA components. The two 24-hour periods were used in a paired analysis to reveal vaccination responses. Temporal trends were classified and collective behavior revealed broad immune-responses captured in saliva, both at the innate as well as the adaptive response time frames.


title: Digital Herd Immunity and COVID-19

text: A population can be immune to epidemics even if not all of its individual members are immune to the disease, just as long as sufficiently many are immune - this is the traditional notion of herd immunity. In the smartphone era a population can be immune to epidemics even if not a single one of its members is immune to the disease - a notion we propose to call "digital herd immunity", which is similarly an emergent characteristic of the population. This immunity arises because contact-tracing protocols based on smartphone capabilities can lead to highly efficient quarantining of infected population members and thus the extinguishing of nascent epidemics. When the disease characteristics are favorable and smartphone usage is high enough, the population is in this immune phase. As usage decreases there is a novel "contact tracing" phase transition to an epidemic phase. We present and study a simple branching-process model for COVID-19 and show that digital immunity is possible regardless of the proportion of non-symptomatic transmission. We believe this is a promising strategy for dealing with COVID-19 in many countries such as India, whose challenges of scale motivated us to undertake this study in the first place and whose case we discuss briefly.


title: T-cell hyperactivation and paralysis in severe COVID-19 infection revealed by single-cell analysis

text: Severe COVID-19 patients can show respiratory failure, T-cell reduction, and cytokine release syndrome (CRS), which can be fatal in both young and aged patients and is a major concern of the pandemic. However, the pathogenetic mechanisms of CRS in COVID-19 are poorly understood. Here we show single cell-level mechanisms for T-cell dysregulation in severe SARS-CoV-2 infection, and thereby demonstrate the mechanisms underlying T-cell hyperactivation and paralysis in severe COVID-19 patients. By in silico sorting CD4+ T-cells from a single cell RNA-seq dataset, we found that CD4+ T-cells were highly activated and showed unique differentiation pathways in the lung of severe COVID-19 patients. Notably, those T-cells in severe COVID-19 patients highly expressed immunoregulatory receptors and CD25, whilst repressing the expression of the transcription factor FOXP3 and interestingly, both the differentiation of regulatory T-cells (Tregs) and Th17 was inhibited. Meanwhile, highly activated CD4+ T-cells express PD-1 alongside macrophages that express PD-1 ligands in severe patients, suggesting that PD-1-mediated immunoregulation was partially operating. Furthermore, we show that CD25+ hyperactivated T-cells differentiate into multiple helper T-cell lineages, showing multifaceted effector T-cells with Th1 and Th2 characteristics. Lastly, we show that CD4+ T-cells, particularly CD25-expressing hyperactivated T-cells, produce the protease Furin, which facilitates the viral entry of SARS-CoV-2. Collectively, CD4+ T-cells from severe COVID-19 patients are hyperactivated and FOXP3-mediated negative feedback mechanisms are impaired in the lung, while activated CD4+ T-cells continue to promote further viral infection through the production of Furin. Therefore, our study proposes a new model of T-cell hyperactivation and paralysis that drives pulmonary damage, systemic CRS and organ failure in severe COVID-19 patients.


title: SEIR Transmission dynamics model of 2019 nCoV coronavirus with considering the weak infectious ability and changes in latency duration

text: Pneumonia patients of 2019-ncov in latent period are not easy to be effectively quarantined, but there is evidence that they have strong infectious ability. Here, the infectious ability of patients during the latent period is slightly less than that of the infected patients was assumed. We established a new SEIR propagation dynamics model, that considered the weak transmission ability of the incubation period, the variation of the incubation period length, and the government intervention measures to track and isolate comprehensively. Based on the raw epidemic data of China from January 23, 2020 to February 10, 2020, the dynamic parameters of the new present SEIR model are fitted. Through the Euler integration algorithm to solve the model, the effect of infectious ability of incubation patients on the theoretical estimation of the present SEIR model was analyzed, and the occurrence time of peak number in China was predicted.


docid: zzfjnhgo

title: Pre-Existing Characteristics Associated with Covid-19 Illness Severity

text: Background. Certain individuals, when infected by SARS-CoV-2, tend to develop more severe forms of Covid-19 illness for reasons that remain unclear. Objective. To determine the demographic and pre-existing clinical characteristics associated with increased severity of Covid-19 infection. Design. Retrospective observational study. We curated data from the electronic health record, and used multivariable logistic regression to examine the association of pre-existing traits with a Covid-19 illness severity defined by level of required care: need for hospital admission, need for intensive care, and need for intubation. Setting. A large, multihospital healthcare system in Southern California. Participants. All patients with confirmed Covid-19 infection (N=442). Results. Of all patients studied, 48% required hospitalization, 17% required intensive care, and 12% required intubation. In multivariable-adjusted analyses, patients requiring a higher levels of care were more likely to be older (OR 1.5 per 10 years, P<0.001), male (OR 2.0, P=0.001), African American (OR 2.1, P=0.011), obese (OR 2.0, P=0.021), with diabetes mellitus (OR 1.8, P=0.037), and with a higher comorbidity index (OR 1.8 per SD, P<0.001). Several clinical associations were more pronounced in younger compared to older patients (Pinteraction<0.05). Of all hospitalized patients, males required higher levels of care (OR 2.5, P=0.003) irrespective of age, race, or morbidity profile. Conclusion. In our healthcare system, greater Covid-19 illness severity is seen in patients who are older, male, African American, obese, with diabetes, and with greater overall comorbidity burden. Certain comorbidities paradoxically augment risk to a greater extent in younger patients. In hospitalized patients, male sex is the main determinant of needing more intensive care. Further investigation is needed to understand the mechanisms underlying these findings.


title: Real-time forecasts and risk assessment of novel coronavirus (COVID-19) cases: A data-driven analysis

text: The coronavirus disease 2019 (COVID-19) has become a public health emergency of international concern affecting 201 countries and territories around the globe. As of April 4, 2020, it has caused a pandemic outbreak with more than 11,16,643 confirmed infections and more than 59,170 reported deaths worldwide. The main focus of this paper is two-fold: (a) generating short term (real-time) forecasts of the future COVID-19 cases for multiple countries; (b) risk assessment (in terms of case fatality rate) of the novel COVID-19 for some profoundly affected countries by finding various important demographic characteristics of the countries along with some disease characteristics. To solve the first problem, we presented a hybrid approach based on autoregressive integrated moving average model and Wavelet-based forecasting model that can generate short-term (ten days ahead) forecasts of the number of daily confirmed cases for Canada, France, India, South Korea, and the UK. The predictions of the future outbreak for different countries will be useful for the effective allocation of health care resources and will act as an early-warning system for government policymakers. In the second problem, we applied an optimal regression tree algorithm to find essential causal variables that significantly affect the case fatality rates for different countries. This data-driven analysis will necessarily provide deep insights into the study of early risk assessments for 50 immensely affected countries.


title: Current status of clinical trial registration regarding coronavirus disease 2019

text: Objective: To summarize the main characteristics of clinical studies regarding coronavirus disease 2019 (COVID-19) registered on the Chinese and US NIH Official Clinical Trial Registration Websites. Methods: To search all the clinical studies about COVID-19 which were registered on the Chinese and U.S. NIH official clinical trial registration websites until March 9, 2020. The search terms were "new coronavirus pneumonia (COVID-19), 2019-nCoV, novel coronavirus pneumonia". Results: Overall, 360 studies with a total sample size of 268, 773 participants are registered on Chinese clinical trial registration website, and 74 studies with a total sample size of 73, 723 participants in the U.S. NIH clinical trial registration website. According to the information provided by the Chinese Clinical Trial Registration Website, there are 237 interventional studies, 108 observational studies, and 15 diagnostic test studies; and the most commonly studied interventions were Traditional Chinese Medicine in 80 studies, antiviral therapy in 58 studies, stem cells in 19 studies, plasma of recovered patients in 13 studies, glucocorticoid in 7 studies, molecular targeted therapy in 4 studies, and vaccine in 2 studies. According to the information provided by the U.S. NIH Clinical Trial Registration Website, there were 54 interventional studies, 17 observational studies, and 3 diagnostic test studies; and the most commonly studied interventions were antiviral therapy in 16 studies, stem cells in 7 studies, Traditional Chinese Medicine in 6 studies, molecular targeted therapy in 3 studies, and vaccine in 3 studies. Conclusions Numerous clinical studies related to COVID-19 have been registered during a very short period. Among them, Traditional Chinese Medicine is the most commonly studied intervention, which suggests the Chinese characteristics in medical care. However, considering such a large sample size needed for these clinical studies, it is very important to ensure the enrollment of participants effectively and orderly in future.


Author rebuttal to response regarding “Letter to the Editor regarding ‘Could pulmonary arterial hypertension patients be at lower risk from severe COVID-19?’”


title: SARS-CoV-2 specific antibody responses in COVID-19 patients

text: A new coronavirus, SARS-CoV-2, has recently emerged to cause a human pandemic. Whereas molecular diagnostic tests were rapidly developed, serologic assays are still lacking, yet urgently needed. Validated serologic assays are important for contact tracing, identifying the viral reservoir and epidemiological studies. Here, we developed serological assays for the detection of SARS-CoV-2 neutralizing, spike- and nucleocapsid-specific antibodies. Using serum samples from patients with PCR-confirmed infections of SARS-CoV-2, other coronaviruses, or other respiratory pathogenic infections, we validated and tested various antigens in different in-house and commercial ELISAs. We demonstrate that most PCR-confirmed SARS-CoV-2 infected individuals seroconverted, as revealed by sensitive and specific in-house ELISAs. We found that commercial S1 IgG or IgA ELISAs were of lower specificity while sensitivity varied between the two, with IgA showing higher sensitivity. Overall, the validated assays described here can be instrumental for the detection of SARS-CoV-2-specific antibodies for diagnostic, seroepidemiological and vaccine evaluation studies.


title: A chest radiography-based artificial intelligence deep-learning model to predict severe Covid-19 patient outcomes: the CAPE (Covid-19 AI Predictive Engine) Model

text: Abstract Keywords: predictive model; prognosis; COVID-19; SARS-CoV-2; Deep-learning; Artificial intelligence; Chest radiograph Background: Chest radiography may be used together with deep-learning models to prognosticate COVID-19 patient outcomes Purpose: To evaluate the performance of a deep-learning model for the prediction of severe patient outcomes from COVID-19 pneumonia on chest radiographs. Methods: A deep-learning model (CAPE: Covid-19 AI Predictive Engine) was trained on 2337 CXR images including 2103 used only for validation while training. The prospective test set consisted of CXR images (n=70) obtained from RT-PCR confirmed COVID-19 pneumonia patients between 1 January and 30 April 2020 in a single center. The radiographs were analyzed by the AI model. Model performance was obtained by receiver operating characteristic curve analysis. Results: In the prospective test set, the mean age of the patients was 46 (+/- 16.2) years (84.2% male). The deep-learning model accurately predicted outcomes of ICU admission/mortality from COVID-19 pneumonia with an AUC of 0.79 (95% CI 0.79-0.96). Compared to traditional risk scoring systems for pneumonia based upon laboratory and clinical parameters, the model matched the EWS and MulBTSA risk scoring systems and outperformed CURB-65. Conclusions: A deep-learning model was able to predict severe patient outcomes (ICU admission and mortality) from COVID-19 on chest radiographs.


docid: jfpbkntx

title: Disease Site-Specific Guidelines for Curative Radiation Treatment During ‘Limited Surgery’ and ‘Hospital Avoidance’: A Radiation Oncology Perspective From the Epicenter of COVID-19 Pandemic

text: The COVID-19 pandemic has resulted in an unprecedented situation where the standard of care (SOC) management for cancers has been altered significantly. Patients with potentially curable cancers are at risk of not receiving timely SOC multidisciplinary treatments, such as surgery, chemotherapy, radiation therapy, or combination treatments. Hospital resources are in such high demand for COVID-19 patients that procedures, such as surgery, dentistry, interventional radiology, and other ancillary services, are not available for cancer patients. Our tertiary care center is considered the center of the epicenter in the USA. As a result, all non-emergent surgeries have been suspended in order to provide hospital beds and other resources for COVID-19 patients. Additionally, ambulatory efforts to avoid treatment-related morbidity are critical for keeping patients out of emergency departments and hospitals. In this review article, we discuss evidence-based radiation therapy approaches for curable cancer patients during the COVID-19 pandemic. We focus on three scenarios of cancer care: 1) radiation therapy as an alternative to surgery when immediate surgery is not possible, 2) radiation therapy as a ‘bridge’ to surgery, and 3) radiation options definitively or postoperatively, given the risk of hospitalization with high-dose chemotherapy.


title: Additive Manufacturing Can Assist in the Fight Against COVID-19 and Other Pandemics and Impact on the Global Supply Chain

text: The high demand on medical devices and personal protective equipment (PPE) during the COVID-19 crisis left millions of health care professionals unprotected in the middle of this situation, as gove


South Africa's coronavirus testing strategy is broken and not fit for purpose: It's time for a change


docid: wxxouetf

title: Estimation of COVID-19 case fatality ratio based on a bi-directional correction method

text: The case fatality rate (CFR) can be used to predict the number of potential deaths in the epidemic and thus can reflect the appropriateness and quality of medical measures developed by public health. When a new disease breaks out, it is particularly important to accurately estimate the CFR. However, while the epidemic is still developing, the crude CFR is often lower than the true value and the hospital CFR is often higher than the true value due to differences in occurrence time, patient number, and treatment plans. Therefore, this study proposes a bi-directional correction method to estimate the CFR. COVID-19 data from China were used to evaluate this method. The results show that this method provides more accurate results than both the crude CFR and hospital CFR. Additionally, this method was used to estimate the CFR of COVID-19 in other countries, with an aim to provide a reference for prevention and control decisions for the COVID-19 epidemic and for the evaluation of medical efforts.


A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)


title: Mitigating COVID-19 outbreak via high testing capacity and strong transmission-intervention in the United States

text: Most models of the COVID-19 pandemic in the United States do not consider geographic variation, and their relevance to public policies is not straightforward. We developed a mathematical model that characterizes infections by state and incorporates inflows and outflows of interstate travelers. Modeling reveals that curbing interstate travel when the disease is already widespread will make little difference. Meanwhile, increased testing capacity (facilitating early identification of infected people and quick isolation) and strict social-distancing and self-quarantine rules are effective in abating the outbreak. The modeling has also produced state-specific information. For example, for New York and Michigan, isolation of persons exposed to the virus needs to be imposed within 2 days to prevent a broad outbreak, whereas for other states this period can be 3.6 days. This model could be used to determine resources needed before safely lifting state policies on social distancing.


title: Protective Adaptive Immunity Against Severe Acute Respiratory Syndrome Coronaviruses 2 (SARS-CoV-2) and Implications for Vaccines

text: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging human coronavirus responsible for coronavirus disease 2019 (COVID-19), a predominantly respiratory disease that has become a global pandemic. Millions of people worldwide are suffering from COVID-19, and hundreds of thousands of those infected have died. Nevertheless, many more people who have been infected with SARS-CoV-2 are asymptomatic or suffer a mild disease characterized by dry cough and mild fever. This new pandemic poses a threat to public health on a global scale, and an intervention to prevent continued spread of SARS-CoV-2 virus is of the utmost importance. To assess preventive and therapeutic strategies, it is imperative to understand the pathogenesis and immune response against SARS-CoV-2. In this review, we concentrate on the protective adaptive immune response elicited by this novel coronavirus as well as requirements for a successful vaccine inducing optimal protection.


The novel Coronavirus (SARS-CoV-2) is a one health issue


title: Development of a data-driven COVID-19 prognostication tool to inform triage and step-down care for hospitalised patients in Hong Kong: A population based cohort study

text: Abstract Background: This is the first study on prognostication in an entire cohort of laboratory-confirmed COVID-19 patients in the city of Hong Kong. Prognostic tool is essential in the contingency response for the next wave of outbreak. This study aims to develop prognostic models to predict COVID-19 patients' clinical outcome on day 1 and day 5 of hospital admission. Methods: We did a retrospective analysis of a complete cohort of 1,037 COVID-19 laboratory-confirmed patients in Hong Kong as of 30 April 2020, who were admitted to 16 public hospitals with their data sourced from an integrated electronic health records system. It covered demographic information, chronic disease(s) history, presenting symptoms as well as the worst clinical condition status, biomarkers' readings and Ct value of PCR tests on Day-1 and Day-5 of admission. The study subjects were randomly split into training and testing datasets in a 8:2 ratio. Extreme Gradient Boosting (XGBoost) model was used to classify the training data into three disease severity groups on Day-1 and Day-5. Results: The 1,037 patients had a mean age of 37.8 (SD {+/-} 17.8), 53.8% of them were male. They were grouped under three disease outcome: 4.8% critical/serious, 46.8% stable and 48.4% satisfactory. Under the full models, 30 indicators on Day-1 and Day-5 were used to predict the patients' disease outcome and achieved an accuracy rate of 92.3% and 99.5%. With a trade-off between practical application and predictive accuracy, the full models were reduced into simpler models with seven common specific predictors, including the worst clinical condition status (4-level), age group, and five biomarkers, namely, CRP, LDH, platelet, neutrophil/lymphocyte ratio and albumin/globulin ratio. Day-1 model's accuracy rate, macro- and micro-averaged sensitivity and specificity were 91.3%, 84.9%-91.3% and 96.0%-95.7% respectively, as compared to 94.2%, 95.9%-94.2% and 97.8%-97.1% under Day-5 model. as compared to 94.2%, 95.0%-97.1% and 98.3%-98.6% under Day-5 model. Conclusions: Both Day-1 and Day-5 models can accurately predict the disease severity. Relevant clinical management could be planned according to the predicted patients' outcome. The model is transformed into a simple online calculator to provide convenient clinical reference tools at the point of care, with an aim to inform clinical decision on triage and step-down care. Keywords: COVID-19, prognostic, prediction, clinical outcome, disease severity, triage, step-down care


Coronavirus symptoms, research chief quits and Nature's plan to join Plan S


title: A collection of designed peptides to target SARS-Cov-2 – ACE2 interaction: PepI-Covid19 database

text: The angiotensin-converting enzyme 2 is the cellular receptor used by SARS coronavirus SARS-CoV and SARS-CoV-2 to enter the cell. Both coronavirus use the receptor-binding domain (RBD) of their viral spike protein to interact with ACE2. The structural basis of these interactions are already known, forming a dimer of ACE2 with a trimer of the spike protein, opening the door to target them to prevent the infection. Here we present PepI-Cov19 database, a repository of peptides designed to target the interaction between the RDB of SARS-CoV-2 and ACE2 as well as the dimerization of ACE2 monomers. The peptides were modelled using our method PiPreD that uses native elements of the interaction between the targeted protein and cognate partner that are subsequently included in the designed peptides. These peptides recapitulate stretches of residues present in the native interface plus novel and highly diverse conformations that preserve the key interactions on the interface. PepI-Covid19 database provides an easy and convenient access to this wealth of information to the scientific community with the view of maximizing its potential impact in the development of novel therapeutic agents.


title: A balance act: minimizing economic loss while controlling novel coronavirus pneumonia

text: The outbreak of Novel Coronavirus Pneumonia (NCP) has significantly affected China and beyond. How to effectively control such epidemic has gradually become a global issue. This paper reviews the economic impact of major epidemics such as SARS, H1N1, and Ebola at the micro-, sector-, and macro-level. The challenge of effective epidemic control is to achieve a balance between viral transmission reduction and economic cost. This paper then summarizes three main methods to evaluate the effectiveness of several control policies. We also find that the adequacy and authenticity of information disclosure is of great importance to minimize economic loss, as either public panic due to overestimation or lack of public awareness due to underestimation can cause additional negative economic impacts. Accurate and transparent disclosure of information plays a crucial role associated with fighting against the epidemic. Finally, the paper puts forward a number of policy recommendations to minimize economic loss while controlling the spread of COVID-19.


title: Aerosol transmission prevention of novel coronavirus in dental clinics/ 口腔诊疗中新型冠状病毒气溶胶传播的防控

text: Corona virus disease 2019 (COVID-19), which broke out in Wuhan, HuBei in December, 2019, spread around the country in a short term. Some infected patients suffered from severe acute respiratory syndrome. It has become a major public health event of international concern. COVID-19 patients are the main source of transmission and most people get infection easily, so the current main prevention method is interrupting the pathway of transmission. The dental treatments are very special because these operations produce substantial aerosols and lead a high risk of cross-infection, which brings challenge for epidemic prevention and control. In this paper, the characteristics of aerosols and prevention methods of aerosol transmission in dental clinics are mainly discussed.


title: Subject Classification

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title: Impact of public health measures to control SARS-CoV-2Outbreak: a data-driven analysis

text: With the rapid spread of the SARS-CoV-2 virus since Fall 2019, governments took variousmeasures to contain the propagation of the pandemic, declared on March, 2020. This study introduces a novel method to estimate the reproductive number using Bayesian inference with time-dependent priors. By inferring the infection dates from incidence time series, the developed approach allows direct comparison between reproductive number and introduction of public health measures in a specific country. First a specific period between the onset of the symptoms and a case being declared as dead is derived on data available in Switzerland. Focussing on the measures taken by 31 European countries, this study shows that most countries required tough state interventions with a stringency index equal to 83.6 out of 100 to reduce the reproductive number below one and hence control the development of the epidemy. In addition, it is shown that there is a direct correlation between the time taken to introduce restrictive measures and the time required to contain the spread of the epidemy with a median time of 8 days between the introduction of initial restrictive measures and the reproductive rate reducing below one.


title: Mapping the Global Research and Clinical Trials in COVID-19

text: COVID-19 has created an unprecedented level of research and innovation activity globally to bring out drug to control or cure the disease, and develop vaccine for long time prevention. A 'new/better normal' is emerging that is trying to push this time period for drug development and vaccine within a year and earlier than that from typical 8 to 10 years for drugs and 10 to 15 years for vaccine. This is happening due to multiple factors: strong policy push by different government that includes dedicated investment, speeding up regulation process, multiple agencies involvement, and multilateral bodies led by WHO trying to create a global platform, huge grants from private funding bodies, strategic linkages across the whole research and innovation value chain between firms, academic, research organisations and start-ups. The paper maps the research papers and ongoing clinical trials to provide an informed view of the current status of the research and drug development activity as seen through the lens of research papers and clinical trials. The intended goal of this study is to help the research community and policy makers to keep track of highly relevant research and drug development in COVID-19.


Orthopedic practice during the Covid-19 crisis in China


title: COVID-19 Detection in Chest X-ray Images using a Deep Learning Approach

text: The Corona Virus Disease (COVID-19) is an infectious disease caused by a new virus that has not been detected in humans before The virus causes a respiratory illness like the flu with various symptoms such as cough or fever that, in severe cases, may cause pneumonia The COVID-19 spreads so quickly between people, affecting to 1,200,000 people worldwide at the time of writing this paper (April 2020) Due to the number of contagious and deaths are continually growing day by day, the aim of this study is to develop a quick method to detect COVID-19 in chest X-ray images using deep learning techniques For this purpose, an object detection architecture is proposed, trained and tested with a public available dataset composed with 1500 images of non-infected patients and infected with COVID-19 and pneumonia The main goal of our method is to classify the patient status either negative or positive COVID-19 case In our experiments using SDD300 model we achieve a 94 92% of sensibility and 92 00% of specificity in COVID-19 detection, demonstrating the usefulness application of deep learning models to classify COVID-19 in X-ray images


title: Structures of potent and convergent neutralizing antibodies bound to the SARS-CoV-2 spike unveil a unique epitope responsible for exceptional potency

text: Understanding the mechanism of neutralizing antibodies (NAbs) against SARS-CoV-2 is critical for effective vaccines and therapeutics development. We recently reported an exceptionally potent NAb, BD-368-2, and revealed the existence of VH3-53/VH3-66 convergent NAbs in COVID-19. Here we report the 3.5-Å cryo-EM structure of BD-368-2’s Fabs in complex with a mutation-induced prefusion-state-stabilized spike trimer. Unlike VH3-53/VH3-66 NAbs, BD-368-2 fully blocks ACE2 binding by occupying all three receptor-binding domains (RBDs) simultaneously, regardless of their “up” and “down” positions. BD-368-2 also triggers fusogenic-like structural rearrangements of the spike trimer, which could impede viral entry. Moreover, BD-368-2 completely avoids the common epitope of VH3-53/VH3-66 NAbs, evidenced by multiple crystal structures of their Fabs in tripartite complexes with RBD, suggesting a new way of pairing potent NAbs to prevent neutralization escape. Together, these results rationalize a unique epitope that leads to exceptional neutralization potency, and provide guidance for NAb therapeutics and vaccine designs against SARS-CoV-2.


title: Epidemic Situation of Novel Coronavirus Pneumonia in China mainland

text: [Objective] Analyze the occurrence of novel coronavirus pneumonia(NCP) in China mainland, explore the epidemiological rules, and evaluate the effect of prevention and control. [Methods] From December 1, 2019 to February 14, 2020, Analysis of 66,492 confirmed cases of NCP in China mainland. [Results] From December 1, 2019 to February 14, 2020, a total of 66,492 cases of NCP were confirmed in China mainland, a total of 54,406 cases were confirmed in Hubei Province, a total of 37,914 cases were confirmed in Wuhan city. On February 5, 2020, the number of suspected cases of NCP in China mainland reached a maximum of 5,328. Since then, the suspected cases have shown a significant downward trend. On February 4, 2020, the number of confirmed cases has gradually decreased in China mainland since then. On February 12, 2020, the number of confirmed cases of NCP in China mainland increased explosively to 15,152, and then began to decline. From February 3, 2020, except for Hubei Province, In China mainland, the number of newly confirmed cases of NCP has continued to decline; From December 1, 2019 to February 14, 2020, a total of 1,523 cases of NCP deaths in China mainland, a cumulative cure of 8096 cases, and mortality and cure rate were 2.29% (1523/66492) and 12.18% (8096/66492) respectively; Starting from January 27, 2020, The spread index of NCP gradually declined, and the extinction index of NCP rose little by little from January 29, 2020. [Conclusion] Starting from February 5, 2020, the number of suspected cases of the NCP is gradually decrease in China mainland. From February 3, 2020, the number of newly confirmed cases of NCP is continuous decline in China mainland except Hubei Province, This shows that the control of the transmission of NCP has achieved. Judged from the number of confirmed cases of NCP, controlling the outbreak in China mainland is to control the epidemic in Hubei province, and the key to controlling the outbreak in Hubei province is to control the epidemic in Wuhan city; Judging from the gradual increase in the number and cure rate of the NCP, and the gradual decline in the number of deaths and mortality, the trend of outbreak control and treatment is getting better; A decrease of the NCP spread index indicates a slowdown in the spread of the virus, but the cumulative confirmed cases is still increase, so the epidemic will continue for some time. However, the turning point of the epidemic in mainland China has not yet occurred. On February 12, 2020, the turning point of the epidemic in China mainland except Hubei province, has turned up.


title: Rapid and accurate detection of novel coronavirus SARS-CoV-2 using CRISPR-Cas3

text: Novel coronavirus SARS-CoV-2 outbreaks have rapidly spread to multiple countries, highlighting the urgent necessity for fast, sensitive, and specific diagnostic tools for virus surveillance. Here, the previously unknown collateral single-stranded DNA cleavage we observed with type I CRISPR-Cas3 highlights its potential for development as a Cas3-mediated rapid (within 40 min), low-cost, instrument-free detection method for SARS-CoV-2. This Cas3-based assay is comparable with Cas12- and real-time reverse-transcriptase PCR-based assays in its speed and sensitivity, but offers greater specificity for single-base-pair discrimination while negating the need for highly trained operators. These findings support the use of CRISPR diagnostics for point-of-care testing in patients with suspected SARS-CoV-2 infections.


title: Systematic Review and Meta-analysis of the Effectiveness and Safety of Hydroxychloroquine in COVID-19.

text: Backgrounds. Since COVID-19 outbreak, various agents have been tested but no proven effective therapies have been identified. This has led to a lot of controversies among associated researches. Hence, in order to address the issue of using hydroxychloroquine in treating COVID-19 patients, we conducted a systematic review and meta-analysis. Methods. A thorough search was carried out to find relevant studies in MEDLINE, medRxiv, PubMed, Cochrane Database, China Academic Journals Full-text Database and Web of Science. Two investigators independently reviewed 274 abstracts and 23 articles. The trials which evaluated hydroxychloroquine for treatment of COVID-19 were included for this systematic review. Two investigators assessed quality of the studies and data extraction was done by one reviewer and cross checked by the other. Results. Five trials involving 677 patients were included while conducting the meta-analysis. Compared with the control group, hydroxychloroquine with or without azithromycin showed benefits in positive-to-negative conversion of SARS-CoV-2 (odds ratio [OR], 1.95 [95% CI,0.19 to 19.73] and a reduction in progression rate (OR, 0.89 [95% CI, 0.58 to 1.37]), but without demonstrating any statistical significance. This systematic review has also suggested a possible synergistic effect of the combination therapy which included hydroxychloroquine and azithromycin. However, the use of hydroxychloroquine alone was associated with increased mortality in COVID-19 patients. Conclusion. The use of hydroxychloroquine with or without azithromycin for treatment of COVID-19 patients, seems to be effective. The combination of hydroxychloroquine and azithromycin has shown synergic effects. However, mortality rate was increased when the treatment was conducted with hydroxychloroquine.


Structure of the nCoV trimeric spike


title: Epitranscriptomic regulation of the response to the air pollutant naphthalene in mouse lungs: from the perspectives of specialized translation and tolerance linked to the writer ALKBH8

text: Background The epitranscriptomic writer Alkylation Repair Homolog 8 (ALKBH8) is a tRNA methyltransferase that modifies the wobble uridine of selenocysteine tRNA to promote the specialized translation, via stop codon recoding, of proteins that contain selenocysteine. Corresponding selenoproteins play critical roles in protecting against reactive oxygen species and environmental stress. Using a novel animal model deficient in Alkbh8, we have investigated the importance of epitranscriptomic systems in the response to naphthalene (NA), an abundant polycyclic aromatic hydrocarbon, glutathione depleter and lung toxicant found in tobacco smoke, gasoline and mothballs. Objectives Our goal was to define the molecular reprogramming of Alkbh8 deficient (Alkbh8def) mice and evaluate the roles that the epitranscriptomic writer ALKBH8 and selenoproteins play in mitigating NA-induced toxicity and lung dysfunction. Methods We performed basal lung analysis and NA exposure studies using WT, Alkbh8def and Cyp2abfgs-null mice, the latter of which lack the cytochrome P450 enzymes required for NA bioactivation. We characterized gene expression, molecular markers of damage, viability and tolerance to NA. Results Under basal conditions, lungs from Alkbh8def mice have increased oxidation-reduction potential (ORP) and 8-isoprostane levels, and have reprogrammed at the molecular level to display increased stress response transcripts. In addition, the ALKBH8 writer deficient lungs have a decreased GSH/GSSG ratio. Alkbh8def mice are more sensitive to NA than WT, showing higher susceptibility to lung damage both at the cellular and molecular levels. WT mice develop a tolerance to NA after 3 days, defined as resistance to a high challenging dose after repeated exposures, which is absent in Alkbh8def mice, with writer deficient not surviving NA exposure. Discussion We conclude that the epitranscriptomic writer ALKBH8 plays a protective role against NA-induced lung dysfunction and promotes NA tolerance. Our work provides an early example of how epitranscriptomic systems can regulate the response to environmental stress in vivo.


Battle against novel coronavirus 2019-nCoV: International commitment to develop worldwide informing campaigns


title: Perceptions and behavioural responses of the general public during the COVID-19 pandemic: A cross-sectional survey of UK Adults

text: Objective: To examine risk perceptions and behavioural responses of the UK adult population during the early phase of the COVID-19 epidemic in the UK. Design: A cross-sectional survey Setting: Conducted with a nationally representative sample of UK adults within 48 hours of the UK Government advising the public to stop non-essential contact with others and all unnecessary travel. Participants: 2,108 adults living in the UK aged 18 years and over. Data were collected between March 17 and 18 2020. Main outcome measures: Descriptive statistics for all survey questions, including the number of respondents and the weighted percentages. Logistic regression was used to identify sociodemographic variation in: (1) adoption of social-distancing measures, (2) ability to work from home, and (3) willingness and (4) ability to self-isolate. Results Overall, 1,992 (94.2%) respondents reported taking at least one preventive measure: 85.8% washed their hands with soap more frequently; 56.5% avoided crowded areas and 54.5% avoided social events. Adoption of social-distancing measures was higher in those aged over 70 compared to younger adults aged 18 to 34 years (aOR:1.9; 95% CI:1.1 to 3.4). Those with the lowest household income were six times less likely to be able to work from home (aOR:0.16; 95% CI:0.09 to 0.26) and three times less likely to be able to self-isolate (aOR:0.31; 95% CI:0.16 to 0.58). Ability to self-isolate was also lower in black and minority ethnic groups (aOR:0.47; 95% CI:0.27 to 0.82). Willingness to self-isolate was high across all respondents. Conclusions The ability to adopt and comply with certain NPIs is lower in the most economically disadvantaged in society. Governments must implement appropriate social and economic policies to mitigate this. By incorporating these differences in NPIs among socio-economic subpopulations into mathematical models of COVID-19 transmission dynamics, our modelling of epidemic outcomes and response to COVID-19 can be improved.


Serious Conditions in COVID-19 Accompanied With a Feature of Metabolic Syndrome


title: Acute liver injury and its association with death risk of patients with COVID-19: a hospital-based prospective case-cohort study

text: Background: Coronavirus disease 2019 (COVID-19) is a newly respiratory infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with multiple organ injuries. The aim of this study was to analyze SARS-CoV-2-induced acute liver injury (ALI), its association with death risk and prognosis after discharge. Methods: Three-hundred and fifty-five COVID-19 patients were recruited. Clinical data were collected from electronic medical records. ALI was evaluated and its prognosis was tracked. The association between ALI and death risk was analyzed. Results: Of 355 COVID-19 patients, 211 were common, 88 severe, and 51 critical ill cases, respectively. On admission, 223 (62.8%) patients were with hypoproteinemia, 151(42.5%) with cholestasis, and 101 (28.5%) with hepatocellular injury. As expected, ALI was more common in critical ill patients. By multivariate logistic regression, male, older age and lymphocyte reduction were three important independent risk factors predicting ALI among COVID-19 patients. Death risk analysis shows that fatality rate was higher among patients with hypoproteinemia than those without hypoproteinemia (RR=9.471, P<0.001). Moreover, fatality rate was higher among patients with cholestasis than those without cholestasis (RR=2.182, P<0.05). Follow-up observation found that more than one hepatic functional indexes of two-third patients remained abnormal 14 days after discharge. Conclusions: ALI at early stage elevates death risk of COVID-19 patients. SARS-CoV-2-induced ALI has not recovered completely 14 days after discharge.


title: Mathematical Model Based COVID-19 Prediction in India and its Different States

text: By employing the successive approximation method to the real-time data of India and its different states, we have predicted the bounds of the spread of COVID-19 in India and its various states. The calculated lower and upper bound of patients (deaths) till 10th June 2020 comes out to be 79496 (3835) and 241759 (7045), respectively. States like Delhi, Gujarat, Maharashtra, Punjab, Rajasthan and Tamil Nadu are the spike states as suggested by the range of expected COVID-19 patients and deaths. Impact of return of stranded pilgrims from Nanded (Maharashtra) has also been looked into in the case of Punjab. It has been found that Punjab may see ~ 5 times increase in the lower bound of expected patients till 10th June 2020 due to the return of pilgrims from Maharashtra. Our study provides an insight into the possible number of expected patients and deaths in near future that may be of importance for the respective governments to be ready with the appropriate preventive measures and logistics to put appropriate infrastructure and medical facilities in place to manage the spread of deadly virus and go down the flattening curve.


title: Comprehensive Transcriptomic Analysis of COVID-19 Blood, Lung, and Airway

text: Abstract SARS-CoV2 is a previously uncharacterized coronavirus and causative agent of the COVID-19 pandemic. The host response to SARS-CoV2 has not yet been fully delineated, hampering a precise approach to therapy. To address this, we carried out a comprehensive analysis of gene expression data from the blood, lung, and airway of COVID-19 patients. Our results indicate that COVID-19 pathogenesis is driven by populations of myeloid-lineage cells with highly inflammatory but distinct transcriptional signatures in each compartment. The relative absence of cytotoxic cells in the lung suggests a model in which delayed clearance of the virus may permit exaggerated myeloid cell activation that contributes to disease pathogenesis by the production of inflammatory mediators. The gene expression profiles also identify potential therapeutic targets that could be modified with available drugs. The data suggest that transcriptomic profiling can provide an understanding of the pathogenesis of COVID-19 in individual patients. Graphical Abstract


title: A model to estimate bed demand for COVID-19 related hospitalization

text: As of March 23, 2020 there have been over 354,000 confirmed cases of coronavirus disease 2019 (COVID-19) in over 180 countries, the World Health Organization characterized COVID-19 as a pandemic, and the United States (US) announced a national state of emergency.1, 2, 3 In parts of China and Italy the demand for intensive care (IC) beds was higher than the number of available beds.4, 5 We sought to build an accessible interactive model that could facilitate hospital capacity planning in the presence of significant uncertainty about the proportion of the population that is COVID-19+ and the rate at which COVID-19 is spreading in the population. Our approach was to design a tool with parameters that hospital leaders could adjust to reflect their local data and easily modify to conduct sensitivity analyses. We developed a model to facilitate hospital planning with estimates of the number of Intensive Care (IC) beds, Acute Care (AC) beds, and ventilators necessary to accommodate patients who require hospitalization for COVID-19 and how these compare to the available resources. Inputs to the model include estimates of the characteristics of the patient population and hospital capacity. We deployed this model as an interactive online tool.6 The model is implemented in R 3.5, RStudio, RShiny 1.4.0 and Python 3.7. The parameters used may be modified as data become available, for use at other institutions, and to generate sensitivity analyses. We illustrate the use of the model by estimating the demand generated by COVID-19+ arrivals for a hypothetical acute care medical center. The model calculated that the number of patients requiring an IC bed would equal the number of IC beds on Day 23, the number of patients requiring a ventilator would equal the number of ventilators available on Day 27, and the number of patients requiring an AC bed and coverage by the Medicine Service would equal the capacity of the Medicine service on Day 21. In response to the COVID-19 epidemic, hospitals must understand their current and future capacity to care for patients with severe illness. While there is significant uncertainty around the parameters used to develop this model, the analysis is based on transparent logic and starts from observed data to provide a robust basis of projections for hospital managers. The model demonstrates the need and provides an approach to address critical questions about staffing patterns for IC and AC, and equipment capacity such as ventilators.


title: Attitudes of multimorbid patients to surviving future acute illness and subsequent functional disability: A systematic review

text: BACKGROUND: Multimorbid patients have worse outcomes following acute hospitalisation. These include increased mortality as an in-patient and after hospital discharge, and increased morbidity and dependence requiring greater use of care facilities. The literature is unclear on the views and wishes of multimorbid patients regarding the outcomes of acute hospitalisation, specifically regarding survival with additional functional disability following acute illness. This is increasingly relevant, with the recent National Institute for Health and Care Excellence (NICE) guidance on admission to hospital and critical care being based on the presence of comorbidities and function as opposed to numerical age. Objectives: We performed a systematic review to assess the current qualitative literature exploring attitudes, wishes and perspectives of adult patients with multimorbidity on surviving future acute illness and subsequent acquired functional disability. METHODS: Eligibility criteria: Eligible studies addressed the attitudes, wishes and perspectives of multimorbid adults to illness and treatment-acquired disability using qualitative methods. Information sources: A search of PubMed, Embase, and CINAHL databases was conducted from database inception through April 2020. References lists from selected papers and NICE Guidelines on Multimorbidity (NG56) were searched iteratively for additional relevant articles. Review methods: Two researchers reviewed candidate full texts independently. Relevant data was extracted to an evidence table. The risk of bias was avoided by adhering to the previously published extensive search strategy and use of qualitative methodology. RESULTS: From 35606 records of which 6370 were duplicates, 20 full texts were reviewed for inclusion, but none met the eligibility criteria. Coverage of domains of importance to multimorbid adults and those highlighted in the NICE guidelines on multimorbidity (NG56) by the 20 short-listed papers was determined; no publications were found to address all domains. DISCUSSION: No studies were identified which have applied appropriate qualitative methodology to understand the wishes, attitudes, and preferences of multimorbid adults regarding treatment and outcomes of acute illness. Such enquiries need to be urgently undertaken to inform and progress policy and clinical practice relating to decisions around admission to hospital and critical care. OTHER: Funding: National Institute of Health Research (NIHR) Research for Patient Benefit grant; NIHR Programme grant; NIHR Doctoral Research Fellowship. Registration: PROSPERO International Prospective Register of systematic reviews (CRD: 42019155028) https://www.crd.york.ac.uk/PROSPERO/


title: Describing the COVID-19 Outbreak - Fitting Modified SIR models to Data

text: In this paper we fit simple modifications of the SIR compartmental model to the COVID-19 outbreak data, available from official sources for Italy and other countries. Even if the complexity of the pandemic can not be easily modelled, we show that our model, at present, describes the time evolution of the data in spite of the application of the social distancing and lock-down procedure. Finally, we discuss the reliability of the model predictions, under certain conditions, for estimating the near and far future evolution of the COVID-19 outbreak. The conditions for the applicability of the proposed models are discussed.


title: Disease experts call for nationwide closure of U.S. schools and businesses to slow coronavirus

text: Infectious disease experts across the United States are calling for tougher enforcement of social distancing measures to slow the spread of the coronavirus behind the COVID-19 pandemic, including a nationwide closure of schools and nonessential businesses Such a move would go beyond the spotty closures now in place in some states and major cities


title: IL-13 Predicts the Need for Mechanical Ventilation in COVID-19 Patients

text: Here we report on an inpatient cohort of COVID-19 positive patients where plasma cytokines were tested for association with future need for mechanical ventilation. Hierarchical clustering, Kaplan-Meier curves, and odds ratios demonstrated that two cytokines, IL-13 (OR: 1.57) and IL-7 (OR: 1.04) and the growth factor bFGF (OR: 1.04), were predictive for intubation.


title: Effect of Alert Level 4 on effective reproduction number: review of international COVID-19 cases

text: The effective reproduction number, Reff, is an important measure of transmission potential in the modelling of epidemics. It measures the average number of people that will be infected by a single contagious individual. A value of Reff > 1 suggests that an outbreak will occur, while Reff< 1 suggests the virus will die out. In response to the COVID-19 pandemic, countries worldwide are implementing a range of intervention measures, such as population-wide social distancing and case isolation, with the goal of reducing Reff to values below one, to slow or eliminate transmission. We analyse case data from 25 international locations to estimate their Reff values over time and to assess the effectiveness of interventions, equivalent to New Zealand's Alert Levels 1-4, for reducing transmission. Our results show that strong interventions, equivalent to NZ's Alert Level 3 or 4, have been successful at reducing Reff below the threshold for outbreak. In general, countries that implemented strong interventions earlier in their outbreak have managed to maintain case numbers at lower levels. These estimates provide indicative ranges of Reff for each Alert Level, to inform parameters in models of COVID-19 spread under different intervention scenarios in New Zealand and worldwide. Predictions from such models are important for informing policy and decisions on intervention timing and stringency during the pandemic.


title: Transcriptomic profiling of disease severity in patients with COVID-19 reveals role of blood clotting and vasculature related genes

text: COVID-19 caused by SARS-CoV-2 manifests as a range of symptoms. Understanding the molecular mechanisms responsible for immuno-pathogenesis of disease is important for treatment and management of COVID-19. We examined host transcriptomes in moderate and severe COVID-19 cases with a view to identifying pathways that affect its progression. RNA extracted from whole blood of COVID-19 cases was analysed by microarray analysis. Moderate and severe cases were compared with healthy controls and differentially regulated genes (DEGs) categorized into cellular pathways. DEGs in COVID-19 cases were mostly related to host immune activation and cytokine signaling, pathogen uptake, host defenses, blood and vasculature genes, and SARS-CoV-2- and other virus- affected pathways. The DEGs in these pathways were increased in severe compared with moderate cases. In a severe COVID-19 patient with an unfavourable outcome we observed dysregulation of genes in platelet homeostasis and cardiac conduction and fibrin clotting with disease progression.


title: Early chest computed tomography to diagnose COVID-19 from suspected patients: A multicenter retrospective study

text: Objective: The purpose of this study is to distinguish the imaging features of COVID-19 with other chest infectious diseases and evaluate diagnostic value of chest CT for suspected patients. Methods: Adult suspected patients aged >18 years within 14 days who underwent chest CT scan and reverse-transcription polymerase-chain-reaction (RT-PCR) tests were enrolled. The enrolled patients were confirmed and grouped according to results of RT-PCR tests. The data of basic demographics, single chest CT features, and combined chest CT features were analyzed for confirmed and non-confirmed groups. Results: A total of 130 patients were enrolled with 54 cases positive and 76 cases negative. The typical CT imaging features of positive group were ground glass opacity (GGO), crazy-paving pattern and air bronchogram. The lesions were mostly distributed bilaterally, close to the lower lungs or the pleura. When features combined, GGO with bilateral pulmonary distribution and GGO with pleural distribution were more common, of which were 31 cases (57.4%) and 30 cases (55.6%) respectively. The combinations were almost presented statistically significant (P<0.05) except for the combination of GGO with consolidation. Most combinations presented relatively low sensitivity but extremely high specificity. The average specificity of these combinations is around 90%. Conclusions: The combinations of GGO could be useful in the identification and differential diagnosis of COVID-19, which alerts clinicians to isolate patients for treatment promptly and repeat RT-PCR tests until incubation ends.


title: Increased expression of ACE2, the SARS-CoV-2 entry receptor, in alveolar and bronchial epithelium of smokers and COPD subjects

text: Rationale: Smokers and patients with chronic obstructive pulmonary disease (COPD) are at increased risk for severe Coronavirus Disease 2019 (COVID-19). Objectives: We investigated the expression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry receptor ACE2 and the protease TMPRSS2 in lung tissue from never smokers and smokers with and without COPD. Methods: In a cross-sectional, observational study we measured mRNA expression of ACE2 and TMPRSS2 by RT-PCR in lung tissue samples from 120 well phenotyped subjects. Next, protein levels of ACE2 were visualized by immunohistochemistry on paraffin sections from 87 subjects and quantified in alveolar and bronchial epithelium. Finally, primary human bronchial epithelial cells (HBECs) were cultured at air liquid interface and exposed to air or cigarette smoke. Results: ACE2 mRNA expression was significantly higher in lung tissue from current smokers and subjects with moderate to very severe COPD and correlated with physiological parameters of airway obstruction and emphysema. Pulmonary expression levels of TMPRSS2 were significantly higher in patients with (very) severe COPD and correlated significantly with ACE2 expression. Importantly, protein levels of ACE2 were elevated in both alveolar and bronchial epithelium of current smokers and subjects with moderate to very severe COPD. Finally, TMPRSS2 mRNA expression increased in in vitro cultured HBECs upon acute exposure to cigarette smoke. Conclusions: We demonstrate increased expression of ACE2 in lungs of smokers and COPD subjects, which might facilitate host cell entry of SARS-CoV-2. These findings help identifying populations at risk for severe COVID-19.


title: Searching an Effective Therapy for the Coronavirus Pandemic: Do We See Light at the End of the Tunnel?

text: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). First reported at the end of December 2019 as a cause for clusters of pneumonia cases in Wuhan city in China, the rapid spread of this condition was declared a pandemic on March 11, 2020, by the World Health Organization (WHO). Apart from the mortality and morbidity associated with COVID-19, the massive social and financial havoc inflicted by this pandemic has left the entire world pondering if medical science can innovate and curtail the ongoing damage due to SARS-CoV-2. Recent findings of an open-label study that investigated the use of hydroxychloroquine and azithromycin in COVID-19 patients in Marseille, France, has garnered some optimism in scientific quarters and the general public alike in terms of finding a treatment regimen to control the rampant rise of COVID-19. We will discuss the potential off-label therapy and studies as it pertains to COVID-19.


title: Chloroquine for treatment of COVID-19 - a pig in a poke?

text: Objective: Chloroquine has been frequently administered for treatment of coronavirus disease 2019 but there are serious concerns about its efficacy and cardiac safety. Our objective was to investigate the pharmacokinetics and safety of chloroquine in hospitalized COVID-19 patients. Design: A prospective observational study. Setting: Dutch hospitals Patients: Patients admitted to the hospital for treatment of COVID-19. Interventions: Pharmacokinetic sampling Measurements: The plasma concentrations of chloroquine and desethylchloroquine and QTc time. Main Results: A total of 83 patients were included. The median (IQR) plasma concentration chloroquine during treatment was 1.05 mol/L (0.63 - 1.55 mol/L). None of the patients reached exposure exceeding the concentration to inhibit SARS-CoV-2 replication by 90% (IC90) of 6.9 M. Furthermore, {Delta}QTc >60 milliseconds occurred after initiation of chloroquine treatment in 34% patients and during treatment QTc [≥]500 milliseconds was observed in 46% of patients. Conclusions: Recommended dose chloroquine treatment results in plasma concentrations that are unlikely to inhibit viral replication. Furthermore, the incidence of QTc prolongation was high. The preclinical promise of chloroquine as antiviral treatment in patients with COVID-19 is overshadowed by its cardiac toxicity and lack of effective exposure. It is unlikely that a positive clinical effect will be found with chloroquine for treatment of COVID-19.


Uncertainty in the Time of Coronavirus


title: Clinical practice guidelines and recommendations in the context of the COVID-19 pandemic: systematic review and critical appraisal

text: Background: The number of published clinical practice guidelines and recommendations related to SARS-CoV-2 infections causing COVID-19 has rapidly increased. However, insufficient consideration of appropriate methodologies in the guideline development could lead to misleading information, uncertainty among professionals, and potentially harmful actions for patients. Purpose: Rapid systematic review of clinical practice guidelines and recommendations in the context of COVID-19 to explore if basic methodological standards of guideline development have been met. Data sources: MEDLINE [PubMed], CINAHL [Ebsco], Trip and manual search; from Feb 1st 2020 until April 27th 2020. Study selection: All types of healthcare workers providing any kind of healthcare to any patient population in any setting. Data extraction: At least two reviewers independently extracted guideline characteristics, conducted critical appraisal according to The Appraisal of Guidelines for Research and Evaluation Instrument (AGREE II) and classified the guidelines using the Association of the Scientific Medical Societies (AWMF) Guidance Manual and Rules for Guideline Development. We plan six-month updates (living review). Data synthesis: There were 1342 titles screened and 188 guidelines included. The highest average AGREE II domain score was 89% for scope and purpose, the lowest for rigor of development (25%). Only eight guidelines (4%) were based on a systematic literature search and a structured consensus process by representative experts (classified as the highest methodological quality, S3 according to AWMF). Patients were only included in the development of one guideline. A process for regular updates was described in 27 guidelines (14%). Limitations: Methodological focus only. Conclusions: Despite clear scope, most publications fell short of basic methodological standards of guideline development. Future research should monitor the evolving methodological quality of the guidelines and their updates over time. Registration/Publication: The protocol was published at www.researchgate.net, DOI: 10.13140/RG.2.2.21293.51689. Preliminary results are publicly available on medRxiv. Funding Source: This study was partly funded by the COVID-19 Rapid Response Funding Scheme of the Wiener Wissenschafts-, Forschungs- und Technologiefonds (WWTF)/Vienna Science and Technology Fund (project number COV20-028). The funding institution had no influence on the results of this work.


title: The Mathematics of Testing with Application to Prevalence of COVID-19

text: We formulate three basic assumptions that should ideally guide any well-designed COVID-19 prevalence study. We provide, on the basis of these assumptions alone, a full derivation of mathematical formulas required for statistical analysis of testing data. In particular, we express the disease prevalence in a population through those for its homogeneous subpopulations. Although some of these formulas are routinely employed in prevalence studies, the study design often contravenes the assumptions upon which these formulas vitally depend. We also designed a natural prevalence estimator from the testing data and studied some of its properties. The results are equally valid for diseases other than COVID-19 as well as in non-epidemiological settings.


title: Total predicted MHC-I epitope load is inversely associated with mortality from SARS-CoV-2

text: Polymorphism in MHC-I protein sequences across human populations significantly impacts their binding to viral peptides and alters T cell immunity to infection. Prioritization of MHC-I restricted viral epitopes remains a fundamental challenge for understanding adaptive immunity to SARS-CoV-2. Here, we present a consensus MHC-I binding prediction model, EnsembleMHC, based on the biochemical and structural basis of peptide presentation to aid the discovery of SARS-CoV-2 MHC-I peptides. We performed immunopeptidome predictions of SARS-CoV-2 proteins across 52 common MHC-I alleles identifying 658 high confidence peptides. Analysis of the resulting peptide-allele assignment distribution demonstrated significant variation across the allele panel up to an order of magnitude. Using MHC-I population-based allele frequencies, we estimated the average SARS-CoV-2 peptide population binding capacity across 21 individual countries. We have discovered a strong inverse association between the predicted population SARS-CoV-2 peptide binding capacity and overall mortality from SARS-CoV-2. Furthermore, we found that the consideration of only structural proteins produced a stronger association with observed death rate, highlighting their importance in protein-targeted immune responses. The 108 predicted SARS-CoV-2 structural protein peptides were shown to be derived from enriched regions in the originating protein, and present minimal risk for disruption by mutation. These results suggest that the immunologic fitness of both individuals and populations to generate class I-restricted T cell immunity to SARS-CoV-2 infection may impact clinical outcome from viral infection.


title: Dynamics of the ACE2 - SARS-CoV/SARS-CoV-2 spike protein interface reveal unique mechanisms

text: The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major public health concern. A handful of static structures now provide molecular insights into how SARS-CoV-2 and SARS-CoV interact with its host target, which is the angiotensin converting enzyme 2 (ACE2). Molecular recognition, binding and function are dynamic processes. To evaluate this, multiple all atom molecular dynamics simulations of at least 500 ns each were performed to better understand the structural stability and interfacial interactions between the receptor binding domain of the spike protein of SARS-CoV-2 and SARS-CoV bound to ACE2. Several contacts were observed to form, break and reform in the interface during the simulations. Our results indicate that SARS-CoV and SARS-CoV-2 utilizes unique strategies to achieve stable binding to ACE2. Several differences were observed between the residues of SARS-CoV-2 and SARS-CoV that consistently interacted with ACE2. Notably, a stable salt bridge between Lys417 of SARS-CoV-2 spike protein and Asp30 of ACE2 as well as three stable hydrogen bonds between Tyr449, Gln493, and Gln498 of SARS-CoV-2 and Asp38, Glu35, and Lys353 of ACE2 were observed, which were absent in the SARS-CoV-ACE2 interface. Some previously reported residues, which were suggested to enhance the binding affinity of SARS-CoV-2, were not observed to form stable interactions in these simulations. Stable binding to the host receptor is crucial for virus entry. Therefore, special consideration should be given to these stable interactions while designing potential drugs and treatment modalities to target or disrupt this interface.


title: Visualizing the COVID-19 pandemic in Bangladesh using coxcombs: A tribute to Florence Nightingale

text: Following detection of the first confirmed case of COVID-19 in early December 2019 in Wuhan, China, nearly six months have passed and almost every country in the world is battling against the COVID-19 war. The frontline warriors, namely the doctors, nurses and healthcare staff, have in many countries struggled to care for the sick under conditions of limited resources and protection and the threat of an overwhelmed healthcare system. It is during times such as this, that we draw strength and inspiration from Florence Nightingale - a passionate statistician, social reformer, feminist champion and a pioneer of modern nursing and data visualization. Nightingale's famed Florence Nightingle Diagram also known as "coxcomb", which was created 150 years ago and used to display the causes of death in the British Army hospital barracks, demonstrated how data visualization techniques could be a powerful medium of communication and a force for change. This paper pays tribute to Nightingale's work by using data from Bangladesh to show that the coxcomb graph is still relevant in the era of COVID-19. The coxcomb graphs that have been produced to display COVID-19 data have provided deeper insights into the trends and relative changes of variables over the course of the pandemic. The paper also describes codes that allow one to easily reproduce the graphs using the statistical programming language R.


title: Pneumococcal Colonisation is an Asymptomatic Event in Healthy Adults using an Experimental Human Colonisation Model

text: Introduction Pneumococcal colonisation is regarded as a pre-requisite for developing pneumococcal disease. In children previous studies have reported colonisation to be a symptomatic event and described a relationship between symptom severity/frequency and colonisation density. The evidence for this in adults is lacking in the literature. This study uses an experimental human pneumococcal challenge model to explore whether pneumococcal colonisation (or co-colonisation with a respiratory virus) is a symptomatic event in healthy adults. Methods Healthy volunteers aged 18-50 were recruited and inoculated intra-nasally with either Streptococcus pneumoniae (serotypes 6B, 23F) or saline as a control. Respiratory viral swabs were obtained prior to inoculation. Nasal and non-nasal symptoms were then assessed using a modified Likert score between 1 (no symptoms) to 7 (cannot function). The rate of symptoms reported between groups was compared and a correlation analysis performed. Results Data from 54 participants were analysed. 46 were inoculated with S. pneumoniae (29 with 6B, 17 with 23F) and 8 received saline. In total, 14 became experimentally colonised (30.4%), all of which were inoculated with 6B serotype. There was no statistically significant difference in nasal (p= 0.45) or non-nasal symptoms (p=0.28) between the pneumococcal inoculation group and the saline group. There was no direct correlation between colonisation density and symptom severity in those who were colonised. In the 22% (12/52) who were co-colonised with pneumococcus and respiratory viruses there was no statistical difference in either nasal or non-nasal symptoms (virus positive p=0.74 and virus negative p=1.0). Conclusion Pneumococcal colonisation is asymptomatic in healthy adults, regardless of bacterial density or viral co-colonisation.


World Bank


title: Higher mortality in men from COVID19 infection-understanding the factors that drive the differences between the biological sexes.

text: The emergent global pandemic caused by the rapid spread of Severe Acute Respiratory syndrome- Coronavirus-2 (SARS-CoV-2) has led to increased mortality and negatively impacted day to day activities of humankind within a short period of time. As the data is rapidly emerging from earlier outbreak locations around the world, there are efforts to assimilate this with the knowledge from prior epidemics and find rapid solutions for this. One of the observations and a recurring theme is the disproportionate differences in the incidence of infection and the consequent mortality between males and females. We, therefore, analyzed retrospective datasets from the previous epidemics and the ongoing pandemic in order to address these differences in clinical outcomes. The data shows that even though the infection rates are similar, the odds ratio of male mortality remains high, indicating a divergence in the crosstalk between the three pathogenic human Coronavirus (hCoVs)- the SARS-CoV, MERS-CoV and the SARS-CoV-2 and immune effectors in the two sexes. One proximate cause is the sex-specific modulation of the X-linked genes that can influence susceptibility to infection. Future studies are needed to confirm these findings, which can form the basis for developing rational strategies for ending the current and preventing future pandemics.


Malaysia: coronavirus, political coup and lockdown


title: Fatigue life prediction of laser and mechanically formed commercially pure grade 2 titanium alloy plates

text: Abstract This paper discusses fatigue life prediction of laser and mechanically formed commercially pure grade 2 titanium alloy plates. It should be noted that predicting fatigue damage for structural components is a complex issue that needs various factors involved in fatigue analysis to be taken into account. This paper looked at available fatigue life prediction theories as a start which then helped formulate and develop the fatigue life prediction analysis used in this study. The predicted fatigue life was not off the mark as it also incorporated the effects of residual stresses which are usually disregarded in studies of this nature. The validity of the fatigue life prediction concept is shown with the aid of calculations versus actual fatigue data results. The results show fatigue life prediction that is stable and less erratic on certain irradiation parameters, while other formed components behaved in a predictable manner. Fatigue life prediction analysis is a challenging undertaking and the behavior of benchmarking components is explained and possible reasons for this elucidated.


title: Estimating the serial interval of the novel coronavirus disease (COVID-19): A statistical analysis using the public data in Hong Kong from January 16 to February 15, 2020

text: Backgrounds: The emerging virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a large outbreak of novel coronavirus disease (COVID-19) in Wuhan, China since December 2019. Based on the publicly available surveillance data, we identified 21 transmission chains in Hong Kong and estimated the serial interval (SI) of COVID-19. Methods: Index cases were identified and reported after symptoms onset, and contact tracing was conducted to collect the data of the associated secondary cases. An interval censored likelihood framework is adopted to fit a Gamma distribution function to govern the SI of COVID-19. Findings: Assuming a Gamma distributed model, we estimated the mean of SI at 4.4 days (95%CI: 2.9−6.7) and SD of SI at 3.0 days (95%CI: 1.8−5.8) by using the information of all 21 transmission chains in Hong Kong. Conclusion: The SI of COVID-19 may be shorter than the preliminary estimates in previous works. Given the likelihood that SI could be shorter than the incubation period, pre-symptomatic transmission may occur, and extra efforts on timely contact tracing and quarantine are recommended in combating the COVID-19 outbreak.


title: Compound climate risks in the COVID-19 pandemic

text: The COVID-19 pandemic will be an unprecedented test of governments’ ability to manage compound risks, as climate hazards disrupt outbreak response around the world Immediate steps can be taken to minimize climate-attributable loss of life, but climate adaptation also needs a long-term strategy for pandemic preparedness


title: SARS-CoV-2 & Pediatric Mental Health: A Review of Recent Evidence

text: SARS-CoV-2 was declared a global pandemic by the World Health Organization (WHO) and was met with lockdown policies to curb the spread of the disease. This meant that 890 million students in 114 countries would be affected by the closure of their educational institutes, affecting their mental health. Mental health disorders are suggested to have a well-correlated link to suicide which is the third most leading cause of death worldwide amongst children aged 15-19 years. According to WHO, 'health is a state of complete physical, mental and social wellbeing and not merely the absence of disease'. Hence the isolation brought about by SARS-CoV-2 is postulated to cause anxiety, fear, and depression amongst the pediatric population, due to the loss of socialization and separation from friends. In this systematic review and meta-analysis, we highlight the major mental health issues in children aged 2-18 years, along with their causes, effects, and potential solutions to tackle these problems.


title: Deteriorated Covid19 control due to delayed lockdown resulting from strategic interactions between Governments and oppositions.

text: Background. In many European countries and the US, the burden of Covid-19 epidemic could be much lower if Governments had been able to learn from the China and Lombardy stories and to declare full lockdown without delays. Methods. We use a simple game-theoretic framework for the strategic interaction between the Government, political oppositions and lobbies, combined with a Covid-19 transmission model, to analyse the role of political factors delaying the lockdown declaration, depending on the degrees of "responsibility" of political actors. Results. The lockdown can always be declared immediately (i.e., without delay) as sustained transmission arises, only if the government feels fully "responsible" towards all citizens. If this is not the case, epidemic growth will eventually dominate the agents' payoffs, so that sooner or later the lockdown will always be declared i.e., both the government and the opposition will be forced by the epidemic to switch towards a higher degree of responsibility, but with a delay. There is a further nontrivial situation where the lockdown can be declared without delay, occurring when the political opposition is at least as responsible as the Government. This however requires the solution of a coordination issue, which cannot be taken for granted. Eventually, a vicious circle emerges, where the delayed lockdown requires a much longer lockdown period to achieve adequate control results, thereby causing the explosion of economic losses and so calling for unlocking long before it should. Conclusions. Lockdown delays have dramatically worsened the impact of the current Covid-19 wave in a number of countries. Citizens should be made cogently aware of this to claim maximal responsibility from political actors and economic lobbies to avoid that such stories repeat in the future when further threats, due to Covid-19 itself or other pathogens, will re-appear.


SARS-CoV-2 in Iceland


title: Predicting clinical needs derived from the COVID-19 pandemic: the case of Spain

text: Background The evolution of the pandemic caused by COVID-19, its high reproductive number and the associated clinical needs, is overwhelming national health systems. We propose a method for predicting both ICU requirements and the number of deaths, and which will enable the health authorities of the countries involved to plan the resources needed to face the pandemic as many days in advance as possible. Methods We use official Spanish data to predict ICU admissions and deaths based on the number of infections. We employ OLS to perform the econometric estimation, and through RMSE, MSE, MAPE, and SMAPE forecast performance measures we select the best lagged predictor of both dependent variables. Findings For Spain, our prediction shows that the best predictor of ICU admissions is the number of people infected eight days before, and that the best predictor of deaths is the number of people infected five days before. In the first case, we obtain a 98% coefficient of determination, and in the second a 97% coefficient. The estimated delayed elasticities find that a 1% increase in the number of cases today will imply a 0.72% increase in ICU patients eight days later and a 1.09% increase in the number of deaths five days later. Interpretation The model is not intended to analyse the epidemiology of COVID-19. Our objective is rather to estimate a leading indicator of clinical needs. Having a forecast model available several days in advance can enable governments to more effectively face the gap between needs and resources triggered by the outbreak and thus reduce the deaths caused by COVID-19.


title: Climate change will drive novel cross-species viral transmission

text: Between 10,000 and 600,000 species of mammal virus are estimated to have the potential to spread in human populations, but the vast majority are currently circulating in wildlife, largely undescribed and undetected by disease outbreak surveillance1,2,3. In addition, changing climate and land use drive geographic range shifts in wildlife, producing novel species assemblages and opportunities for viral sharing between previously isolated species4,5. In some cases, this will inevitably facilitate spillover into humans6,7—a possible mechanistic link between global environmental change and emerging zoonotic disease8. Here, we map potential hotspots of viral sharing, using a phylogeographic model of the mammal-virus network, and projections of geographic range shifts for 3,870 mammal species under climate change and land use scenarios for the year 2070. Shifting mammal species are predicted to aggregate at high elevations, in biodiversity hotspots, and in areas of high human population density in Asia and Africa, sharing novel viruses between 3,000 and 13,000 times. Counter to expectations, holding warming under 2°C within the century does not reduce new viral sharing, due to greater range expansions—highlighting the need to invest in surveillance even in a low-warming future. Most projected viral sharing is driven by diverse hyperreservoirs (rodents and bats) and large-bodied predators (carnivores). Because of their unique dispersal capacity, bats account for the majority of novel viral sharing, and are likely to share viruses along evolutionary pathways that could facilitate future emergence in humans. Our findings highlight the urgent need to pair viral surveillance and discovery efforts with biodiversity surveys tracking range shifts, especially in tropical countries that harbor the most emerging zoonoses.


title: CT in relation to RT-PCR in diagnosing COVID-19 in the Netherlands: a prospective study

text: Introduction Early differentiation between emergency department (ED) patients with and without corona virus disease (COVID-19) is very important. Chest CT scan may be helpful in early diagnosing of COVID-19. We investigated the diagnostic accuracy of CT using RT-PCR for SARS-CoV-2 as reference standard and investigated reasons for discordant results between the two tests. Methods In this prospective single centre study in the Netherlands, all adult symptomatic ED patients had both a CT scan and a PCR upon arrival at the ED. CT results were compared with PCR test(s). Diagnostic accuracy was calculated. Discordant results were investigated using discharge diagnoses. Results Between March 13th and March 24th 2020, 193 symptomatic ED patients were included. In total, 43.0% of patients had a positive PCR and 56.5% a positive CT, resulting in a sensitivity of 89.2%, specificity 68.2%, likelihoodratio (LR) + 2.81 and LR- 0.16. Sensitivity was higher in patients with high risk pneumonia (CURB-65 score ≥3; n=17, 100%) and with sepsis (SOFA score ≥2; n=137, 95.5%). Of the 35 patients (31.8%) with a suspicious CT and a negative PCR, 9 had another respiratory viral pathogen, and in 7 patients, COVID-19 was considered likely. One of nine patients with a non-suspicious CT and a positive PCR had developed symptoms within 48 hours before scanning. Discussion The accuracy of chest CT in symptomatic ED patients is high, but used as a single diagnostic test, CT can not safely diagnose or exclude COVID-19. However, CT can be used as a quick first screening tool.


title: Genetic structure of SARS-CoV-2 in Western Germany reflects clonal superspreading and multiple independent introduction events

text: We whole-genome sequenced 55 SARS-CoV-2 isolates from Western Germany and investigated the genetic structure of SARS-CoV-2 outbreaks in the Heinsberg district and Dusseldorf. While the genetic structure of the Heinsberg outbreak indicates a clonal origin, reflective of superspreading dynamics during the carnival season, distinct viral strains are circulating in Dusseldorf, reflecting the city's international links. Limited detection of Heinsberg strains in the Dusseldorf area despite geographical proximity may reflect efficient containment and contact tracing efforts.


An 'asymptomatic' driver with COVID-19: Atypical suspected myocarditis by SARS-CoV-2


title: A generalized action plan for obstetric hospitals and outpatient clinics during the suspected or confirmed COVID-19 pandemic

text: This summary paper presents a generalized action plan for hospitals and outpatient clinics during the COVID-19 coronavirus pandemic. Now the pandemic is the most relevant global challenge. Taking into account that the medical world does not have much clinical experience with COVID-19 and other coronaviruses, such as SARS-CoV and MERS-CoV, thoroughness and caution in assessing and treating pregnant women is an extremely urgent topic. The authors of this article summarized the world experience in managing patients with coronavirus disease and brought it into a unique algorithm that was considered most rational.


Could the Inhibition of Endo-Lysosomal Two-Pore Channels (TPCs) by the Natural Flavonoid Naringenin Represent an Option to Fight SARS-CoV-2 Infection?


title: “Innovation from Dentistry” -Seeds derived from the clinical dentistry

text: The authors would like to introduce the invention, derived from the research on denture plaque, applied to a wide variety of items Firstly, we found L rhamnosus L8020, as one of the normal strains of bacteria in the oral cavity and have shown to have inhibitory activity against a broad spectrum of bacteria causing dental caries and periodontal disease, in addition to oral Candida Based upon the patents on L rhamnosus L8020, several products incorporated with L8020, like mouthwash, dentifrice, tablets and chocolate, in addition to yoghurt, have been commercialized Secondly, we developed the organosilicon quaternary ammonium salts [3-(triethoxysilyl) - propyldimethyl- octadecyl ammonium chloride (Etak), a coupling agent with disinfectant It has broad spectrum antimicrobial activity against both Gram-positive and –negative bacteria, fungi and yeasts, in addition to envelope virus, like influenza and corona virus This compound binds chemically to a variety substrates, making it a nonleachable antibacterial and antiviral agent Its bounded antimicrobial activity has had a variety of applications by binding to fibers, fabric, carpet, sock manufactures (to control odor-causing bacteria), and metal surfaces The effects will be contributed to the suppression of a variety of infectious diseases, including flu and covid-19 Mikihouse, Dinos, AOKI, Esai company has been commercialized a variety of items, based upon our patents This paper described the examples that intellectual property based upon innovations from prosthodontic research have been utilized by general companies, and yielded the living ware


title: A rapid, point of care red blood cell agglutination assay for detecting antibodies against SARS-CoV-2

text: The COVID-19 pandemic has brought the world to a halt, with cases observed around the globe causing significant mortality. There is an urgent need for serological tests to detect antibodies against SARS-CoV-2, which could be used to assess the prevalence of infection, as well as ascertain individuals who may be protected from future infection. Current serological tests developed for SARS-CoV-2 rely on traditional technologies such as enzyme-linked immunosorbent assays (ELISA) and lateral flow assays, which may lack scalability to meet the demand of hundreds of millions of antibody tests in the coming year. Herein, we present an alternative method of antibody testing that just depends on one protein reagent being added to patient serum/plasma or whole blood and a short five-minute assay time. A novel fusion protein was designed that binds red blood cells (RBC) via a single-chain variable fragment (scFv) against the H antigen and displays the receptor-binding domain (RBD) of SARS-CoV-2 spike protein on the surface of RBCs. Upon mixing of the fusion protein, RBD-scFv with recovered COVID-19 patient serum and RBCs, we observed agglutination of RBCs, indicating the patient developed antibodies against SARS-CoV-2 RBD. Given that the test uses methods routinely used in hospital clinical labs across the world, we anticipate the test can be rapidly deployed with only the protein reagent required at projected manufacturing cost at U.S. cents per test. We anticipate our agglutination assay may find extensive use in low-resource settings for detecting SARS-CoV-2 antibodies.


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title: COVID-19 and patient-doctor confidentiality

text: Given the increasing numbers of ethical and legal issues arising from the COVID-19 epidemic, particularly in respect of patient-doctor confidentiality, doctors must explain to patients how the measures taken to combat the spread of the virus impact on their confidentiality Patients must be reassured that doctors are ethically bound to continue to respect such confidentiality, but it should be made clear to them that doctors must also comply with the demands of the law While the Constitution, statutory law and the common law all recognise a person's right to privacy, during extraordinary times such as the COVID-19 pandemic, confidentiality must be breached to a degree to halt the spread of the virus


Does air pollution influence COVID-19 outbreaks?


title: Neonatal Coronavirus 2019 (COVID-19) Infection: A Case Report and Review of Literature

text: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global pandemic affecting 213 countries as of April 26, 2020. Although this disease is affecting all age groups, infants and children seem to be at a lower risk of severe infection, for reasons unknown at this time. We report a case of neonatal infection in New York, United States, and provide a review of the published cases. A 22-day-old, previously healthy, full-term neonate was hospitalized after presenting with a one-day history of fever and poor feeding. Routine neonatal sepsis evaluation was negative. SARS-CoV-2 polymerase chain reaction (PCR) testing was obtained, given rampant community transmission, which returned positive. There were no other laboratory or radiographic abnormalities. The infant recovered completely and was discharged home in two days once his feeding improved. The family was advised to self-quarantine to prevent the transmission of COVID-19. We believe that the mode of transmission was horizontal spread from his caregivers. This case highlights the milder presentation of COVID-19 in otherwise healthy, full-term neonates. COVID-19 must be considered in the evaluation of a febrile infant. Infants and children may play an important role in the transmission of COVID-19 in the community. Hence, with an understanding of the transmission patterns, parents and caregivers would be better equipped to limit the spread of the virus and protect the more vulnerable population.


title: Maternal blood lipidomics analyses link critical metabolic pathways associated with severe preeclampsia

text: Preeclampsia is a pregnancy specific syndrome characterized by hypertension and proteinuria after 20 weeks of gestation. To reveal the relationship between lipids and preeclampsia, we conduct lipidomic profiling of maternal serums of 44 severe preeclamptic and 20 healthy pregnancies from a multi-ethnic cohort in Hawaii. Correlation network analysis shows that oxidized phospholipids (OxPLs) have increased inter-correlations and connections in preeclampsia, while other lipids, including triacylglycerols (TAGs), have reduced network correlations and connections. Thirty-one lipid species from various lipid classes demonstrate predominantly reductions and causal relationships with preeclampsia. They include phosphatidylglycerol (PG), TAG, diacylglycerol (DAG), phosphatidylcholine (PC), cholesterol esters (CE), phosphatidylethanolamine (PE), sphingomyelin (SM), ceramides (Cer-NS), hexosyl ceramides (HexCer-NS), lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), and free fatty acid (FFA). Many of these lipids are also selected as important features by a linear discriminant analysis (LDA) classifier with high predictive accuracy (F-1 statistic 0.941 and balanced accuracy 0.88), indicating their potential to serve as biomarkers for severe preeclampsia. Our study supports the hypothesis of a phospholipid (PL) centered, dysregulated lipidomic metabolic atlas. That is, severe preeclampsia may be originated from hypoxia, which induces the accumulation of OxPLs through oxidative stress whereas reduces many other lipids (eg. reduced PCs, TAGs and ceramides). These molecular changes coherently lead to dysregulated biological functions, such as insulin signaling and inflammation/infections. Moreover, the lipid changes may also be responsible for the comorbidity between preeclampsia and gestational diabetes, a clinically known risk factor for preeclampsia.