title: SARS-CoV-2 mutations altering regulatory properties: deciphering host’s and virus’s perspectives

text: Since the first recorded case of the SARS-CoV-2, it has acquired several mutations in its genome while spreading throughout the globe. However, apart from some changes in protein coding, functional importance of these mutations in disease pathophysiology are still largely unknown. In this study, we investigated the significance of these mutations both from the host’s and virus’s perspective by analyzing the host miRNA binding and virus’s internal ribosome entry site (IRES), respectively. Strikingly, we observed that due to the acquired mutations, host miRNAs bind differently compared to the reference; where few of the miRNAs lost and few gained the binding affinity for targeting the viral genome. Moreover, functional enrichment analysis suggests that targets of both of these gained and lost miRNAs might be involved in various host immune signaling pathways. Also, we sought to shed some insights on the impacts of mutations on the IRES structure of SARS-CoV-2. Remarkably, we detected that three particular mutations in the IRES can disrupt its secondary structure which can further make the virus less functional. These results could be valuable in exploring the functional importance of the mutations of SARS-CoV-2 and could provide novel insights into the differences observed different parts of the world.


title: Lost and Found: Stopping Bluetooth Finders from Leaking Private Information

text: A Bluetooth finder is a small battery-powered device that can be attached to important items such as bags, keychains, or bikes. The finder maintains a Bluetooth connection with the user's phone, and the user is notified immediately on connection loss. We provide the first comprehensive security and privacy analysis of current commercial Bluetooth finders. Our analysis reveals several significant security vulnerabilities in those products concerning mobile applications and the corresponding backend services in the cloud. We also show that all analyzed cloud-based products leak more private data than required for their respective cloud services. Overall, there is a big market for Bluetooth finders, but none of the existing products is privacy-friendly. We close this gap by designing and implementing PrivateFind, which ensures locations of the user are never leaked to third parties. It is designed to run on similar hardware as existing finders, allowing vendors to update their systems using PrivateFind.


title: Reverse transcription loop-mediated isothermal amplification combined with nanoparticles-based biosensor for diagnosis of COVID-19

text: Given the scale and rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, known as 2019-nCov) infection (COVID-19), the ongoing global SARS-CoV-2 outbreak has become a huge public health issue. Rapid and precise diagnostic methods are thus immediately needed for diagnosing COVID-19, providing timely treatment and facilitating infection control. A one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP) coupled with nanoparticles-based biosensor (NBS) assay (RT-LAMP-NBS) was successfully established for rapidly and accurately diagnosing COVID-19. A simple equipment (such as heating block) was required for maintaining a constant temperature (63 C) for only 40 min. Using two designed LAMP primer sets, F1ab (opening reading frame 1a/b) and np (nucleoprotein) genes of SARS-CoV-2 were simultaneously amplified and detected in a one-step and single-tube reaction, and the detection results were easily interpreted by NBS. The sensitivity of SARS-CoV-2 RT-LAMP-NBS was 12 copies (each of detection target) per reaction, and no cross-reactivity was generated from non-SARS-CoV-2 templates. Among clinically diagnosed COVID-19 patients, the analytical sensitivity of SARS-CoV-2 was 100% (33/33) in the oropharynx swab samples, and the assay's specificity was also 100% (96/96) when analyzed the clinical samples collected from non-COVID-19 patients. The total diagnosis test from sample collection to result interpretation only takes approximately 1 h. In sum, the RT-LAMP-NBS is a promising tool for diagnosing the current SARS-CoV-2 infection in first line field, public health and clinical laboratories, especially for resource-challenged regions.


title: The Longevity-Frailty Hypothesis: Evidence from COVID-19 Death Rates in Europe

text: COVID-19 death rates vary strikingly across Europe. The death rate in Spain, for example, is greater than the death rate in Germany by more than a factor of ten. Few if any epidemiological indicators distinguish the countries of Europe by such a vast margin. Evidence on age-specific case-fatality rates (deaths over observed infections) and age-specific death rates (deaths over population) indicate that COVID-19 disproportionately afflicts the elderly and frail, suggesting that the share of elderly population (≥ 65 years of age) in a country ought to be a strong predictor of the COVID-19 death rate. However, the COVID-19 death rate and the share of elderly population are statistically uncorrelated (r = 0.163, p = 0.399). Share of population ≥ 65 years of age is confounded by mortality selection, as well as other demographic dynamics. By contrast, elderly longevity or life expectancy at 65 more effectively captures population survival and the accumulation of age-related frailty in society. We find a strong statistical relationship between the COVID-19 death rate (r = 0.839, p < .001) and elderly longevity, and a moderately strong relationship between the date of epidemic timing and elderly longevity (r = −0.634, p < .001). These relationships are robust to the inclusion of statistical controls for international tourism inflow and hospital bed capacity. While the countries of Europe vary meaningfully in healthcare system capacity and in the timing and intensity of non-pharmaceutical interventions, the striking variation in COVID-19 death rates across these countries is statistically and intuitively associated with elderly survival and consequent frailty.


title: Saliva as a non-invasive sample for the detection of SARS-CoV-2: a systematic review

text: The accepted gold standard for diagnosing coronavirus disease (COVID-19) is the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA from nasopharyngeal swabs (NPS). However, shortage of reagents has made NPS collection challenging, and alternative samples need to be explored. Due to its non-invasive nature, saliva has considerable diagnostic potential. Therefore, to guide diagnostic laboratories globally, we conducted a systematic review to determine the utility of saliva for the detection of SARS-CoV-2. A systematic search of major databases (PubMed, ISI Web of Science, Scopus, and Google Scholar) was performed to identify published studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. There was a total of 10 publications that fit the criteria for review. Most studies collected drooled whole saliva from hospitalized patients or pipetted saliva from intubated patients. Saliva was positive in 31-92% of patients depending on the cohort and length of hospitalization. Viral loads in saliva are comparable to those in NPS and ranged from 9.9 x 10^2 to 1.2 x 10^8 copies/mL during the first week of symptoms and decrease over time. Saliva can be positive up to 20 days post-symptom onset with viral loads correlating with symptom severity and degree of tissue damage. Based on these findings, we made suggestions to guide the clinical laboratory and suggest the need for diagnostic accuracy studies for the detection of SARS-CoV-2 from saliva.


docid: rfxsotix

title: Identifying main and interaction effects of risk factors to predict intensive care admission in patients hospitalized with COVID-19: a retrospective cohort study in Hong Kong

text: Background: The coronavirus disease 2019 (COVID-19) has become a pandemic, placing significant burdens on the healthcare systems. In this study, we tested the hypothesis that a machine learning approach incorporating hidden nonlinear interactions can improve prediction for Intensive care unit (ICU) admission. Methods: Consecutive patients admitted to public hospitals between 1st January and 24th May 2020 in Hong Kong with COVID-19 diagnosed by RT-PCR were included. The primary endpoint was ICU admission. Results: This study included 1043 patients (median age 35 (IQR: 32-37; 54% male). Nineteen patients were admitted to ICU (median hospital length of stay (LOS): 30 days, median ICU LOS: 16 days). ICU patients were more likely to be prescribed angiotensin converting enzyme inhibitors/angiotensin receptor blockers, anti-retroviral drugs lopinavir/ritonavir and remdesivir, ribavirin, steroids, interferon-beta and hydroxychloroquine. Significant predictors of ICU admission were older age, male sex, prior coronary artery disease, respiratory diseases, diabetes, hypertension and chronic kidney disease, and activated partial thromboplastin time, red cell count, white cell count, albumin and serum sodium. A tree-based machine learning model identified most informative characteristics and hidden interactions that can predict ICU admission. These were: low red cells with 1) male, 2) older age, 3) low albumin, 4) low sodium or 5) prolonged APTT. A five-fold cross validation confirms superior performance of this model over baseline models including XGBoost, LightGBM, random forests, and multivariate logistic regression. Conclusions: A machine learning model including baseline risk factors and their hidden interactions can accurately predict ICU admission in COVID-19.


title: Rapid evidence summary on SARS-CoV-2 survivorship and disinfection, and a reusable PPE protocol using a double-hit process

text: In the COVID-19 pandemic caused by SARS-CoV-2, hospitals are stretched beyond capacity. There are widespread reports of dwindling supplies of personal protective equipment (PPE), which are paramount to protect frontline medical/nursing staff and to minimize further spread of the virus. We carried out a rapid review to summarize the existing evidence on SARS-CoV-2 survivorship and methods to disinfect PPE gear, particularly N95 filtering facepiece respirators (FFR). In the absence of data on SARS-CoV-2, we focused on the sister virus SARS-CoV-1. We propose a two-step disinfection process, which is conservative in the absence of robust evidence on SARS-CoV-2. This disinfection protocol is based on an initial storage of PPE for ≥4 days, followed by ultraviolet light (UVC), dry heat treatment, or chemical disinfection. Importantly, each of the two steps is based on independent disinfection mechanisms, so that our proposed protocol is a multiplicative system, maximising the efficacy of our disinfection process. This method could be rapidly implemented in other healthcare settings, while testing of each method is undertaken, increasing the frontline supply of PPE, and avoiding many of the upstream issues of supply chain disruption currently being faced.


title: The 2020 COVID-19 Pandemic: Front Line Perspectives through Different Lenses

text: Factual news and information surrounding the 2020 SARS-CoV-2, COVID-19 pandemic are plentiful, but the perspectives of doctors on the front lines illuminate the impact of the disease. Confronting the same threat, this “Perspectives” series reveals the motivations, inner fears, and insights across the spectrum of academic Emergency Medicine physicians including a medical student, resident, faculty educator, chair, and emeritus faculty. While the individual challenges may appear to be very different, there is a consistency in the underlying message, one that underscores the unrelenting commitment of emergency physicians to serve their communities, innovate, and support one another.


title: Lyophilized Matrix Containing Ready-to-Use Primers and Probe Solutions for Standardization of Real-Time PCR and RT-qPCR Diagnostics

text: Real-time molecular techniques have become the reference methods for the direct diagnosis of pathogens The reduction of steps is a key factor in order to decrease the risk of human errors resulting in invalid series and delayed results We describe here a process involving the preparation of oligonucleotide primers and a hydrolysis probe in a single tube at predefined optimized concentrations that are stabilized via lyophilization (Lyoph-P&P) Lyoph-P&P was compared to the classic protocol using extemporaneously prepared liquid reagents, assaying (i) sensitivity, (ii) long-term stability at 4 °C, and (iii) long-term stability at 37 °C, mimicking transportation without a cold chain Two previously published molecular assays were selected for this study They target two emerging viruses that are listed on the blueprint of the WHO to be considered for preparedness and response actions: chikungunya virus (CHIKV) and Rift Valley fever phlebovirus (RVFV) The results of our study demonstrate that (i) Lyoph-P&P is stable for at least four days at 37 °C, supporting shipping without the need of a cold chain, (ii) Lyoph-P&P rehydrated solution is stable at 4 °C for at least two weeks, (iii) the sensitivity observed with Lyoph-P&P is at least equal to, and often better than, that observed with liquid formulation, and (iv) the validation of results observed with low-copy specimens is rendered easier by higher fluorescence levels In conclusion, Lyoph-P&P holds several advantages over extemporaneously prepared liquid formulations and merits consideration as a novel real-time molecular assay for implementation into a laboratory with routine diagnostic activity Since the meeting, this concept has been applied to the COVID-19 situation: two diagnostic assays (E gene and RdRp) have been developed and can be ordered on the European Virus Archive catalog (https://www european-virus-archive com/detection-kit/lyophilized-primers-and-probe-rt-pcr-2019-ncov-e-gene;https://www european-virus-archive com/detection-kit/lyophilized-primers-and-probe-rt-pcr-sars-cov-2-rdrp-gene)


Como el COVID-19 pandemia afecta nuestra actividad como cirujanos traumatólogos


title: Bulk and single-cell transcriptomics identify tobacco-use disparity in lung gene expression of ACE2, the receptor of 2019-nCov

text: In current severe global emergency situation of 2019-nCov outbreak, it is imperative to identify vulnerable and susceptible groups for effective protection and care. Recently, studies found that 2019-nCov and SARS-nCov share the same receptor, ACE2. In this study, we analyzed five large-scale bulk transcriptomic datasets of normal lung tissue and two single-cell transcriptomic datasets to investigate the disparities related to race, age, gender and smoking status in ACE2 gene expression and its distribution among cell types. We didn't find significant disparities in ACE2 gene expression between racial groups (Asian vs Caucasian), age groups (>60 vs <60) or gender groups (male vs female). However, we observed significantly higher ACE2 gene expression in former smoker's lung compared to non-smoker's lung. Also, we found higher ACE2 gene expression in Asian current smokers compared to non-smokers but not in Caucasian current smokers, which may indicate an existence of gene-smoking interaction. In addition, we found that ACE2 gene is expressed in specific cell types related to smoking history and location. In bronchial epithelium, ACE2 is actively expressed in goblet cells of current smokers and club cells of non-smokers. In alveoli, ACE2 is actively expressed in remodelled AT2 cells of former smokers. Together, this study indicates that smokers especially former smokers may be more susceptible to 2019-nCov and have infection paths different with non-smokers. Thus, smoking history may provide valuable information in identifying susceptible population and standardizing treatment regimen.


A return to class solidarity


title: The efficiency in the ordinary hospital bed management in Italy: an in-depth analysis of intensive care unit in the areas affected by COVID-19 before the outbreak

text: In the first months of 2020 an increasing number of individuals worldwide are infected by the coronavirus disease 2019 (COVID-19). A particularly severe diffusion of the virus has affected Italy and in particular its northern regions. This is resulting in a high demand of hospitalization with a particular attention on the intensive care units (ICUs). Hospitals are suffering the high degree of patients to be treated for respiratory diseases and the majority of the structures located in the north of Italy are or are going to be saturated. This has led the actual and past national and regional governments to be heavily criticized for reducing in the past years the number of beds, in particular those located in the ICUs across the country. Aim of this study is to analyse the availability of hospital beds across the country as well as to determine their management in terms of complexity and performance of cases treated at regional level. The results of this study underlines that, despite the reduction of beds for the majority of the hospital wards, ICUs availabilities did not change between 2010 and 2017. Moreover, this study confirms that the majority of the Italian regions efficiently manage these structural facilities allowing hospitals to treat patients without the risk of having an overabundance of patients and a scarcity of beds. In fact, this analysis shows that, in normal situations, the management of hospital and intensive care beds has no critical levels.


title: The paradox of trust: perceived risk and public compliance during the COVID-19 pandemic in Singapore

text: Public trust in the authorities has been recognised in risk research as a crucial component of effective and efficient risk management. But in a pandemic, where the primary responsibility of risk management is not centralised within institutional actors but defused across society, trust can become a double-edged sword. Under these conditions, public trust based on a perception of government competence, care and openness may in fact lead people to underestimate risks and thus reduce their belief in the need to take individual action to control the risks. In this paper, we examine the interaction between trust in government, risk perceptions and public compliance in Singapore in the period between January and April 2020. Using social media tracking and online focus group discussions, we present a preliminary assessment of public responses to government risk communication and risk management measures. We highlight the unique deployment of risk communication in Singapore based on the narrative of ‘defensive pessimism’ to heighten rather than lower levels perceived risk. But the persistence of low public risk perceptions and concomitant low levels of compliance with government risk management measures bring to light the paradox of trust. This calls for further reflection on another dimension of trust which focuses on the role of the public; and further investigation into other social and cultural factors that may have stronger influence over individual belief in the need to take personal actions to control the risks.


title: Impact of essential workers in the context of social distancing for epidemic control

text: Many governments have responded to the ongoing COVID-19 pandemic by imposing social policies that restrict interactions outside of the home, resulting in a large fraction of the workforce either working from home or not working. However, to maintain essential services, a substantial number of workers are not subject to these limitations, and maintain many of their pre-intervention interactions. To explore how interactions among such "essential" workers, and between essential workers and the rest of the population, impact disease risk and the effectiveness of pandemic control, we evaluated several models of essential worker interactions within a standard epidemiology framework. The models were designed to correspond to key characteristics of, respectively, cashiers, factory employees, and healthcare workers. We find in all three models that essential workers are at substantially elevated risk of infection compared to the rest of the population, and that increasing the numbers of essential workers necessitates the imposition of more stringent interaction controls on the rest of the population in order to manage the pandemic. However, different archetypes of essential workers differ in both their individual probability of infection and impact on the broader pandemic, highlighting the need to understand and target for intervention the specific risks faced by different groups of essential workers.


title: Determination of Robust Regional CT Radiomics Features for COVID-19

text: Background: The lung CT images of COVID-19 patients can be characterized by three different regions: Ground Glass Opacity (GGO), consolidation and pleural effusion. GCOs have been shown to precede consolidations. Quantitative characterization of these regions using radiomics can facilitate accurate diagnosis, disease progression and response to treatment. However, according to the knowledge of the author, regional CT radiomics analysis of COVID-19 patients has not been carried out. This study aims to address these by determining the radiomics features that can characterize each of the regions separately and can distinguish the regions from each other. Methods: 44 radiomics features were generated with four quantization levels for 23 CT slice of 17 patients. Two approaches were the implemented to determine the features that can differentiate between lung regions: 1) Z-score and correlation heatmaps and 2) one way ANOVA for finding statistically significantly difference (p<0.05) between the regions. Radiomics features that show agreement for all cases (Z-score, correlation and statistical significant test) were selected as suitable features. The features were then tested on 52 CT images. Results: 10 radiomics features were found to be the most suitable among 44 features. When applied on the test images, they can differentiate between GCO, consolidation and pleural effusion successfully and the difference provided by these 10 features between three lung regions are statistically significant. Conclusion: The ten robust radiomics features can be useful in extracting quantitative data from CT lung images to characterize the disease in the patient, which in turn can help in more accurate diagnosis, staging the severity of the disease and allow the clinician to plan for more successful personalized treatment for COVID-19 patients. They can also be used for monitoring the progression of COVID-19 and response to therapy for clinical trials.


title: Impact of COVID-19 pandemic on organization of religious behaviour in different christian denominations in Poland

text: Any pandemic disorganizes the life of wider society. One of the manifestations of social activity is religious life. Despite progressing secularization, both religion, churches, and denominational associations have an impact on individual ethical choices and business decisions. This is true especially in Poland, where over 90 percent of the citizens declare affiliation with some religion, mostly Christian. The purpose of the present article is to demonstrate what activities are undertaken by churches in Poland at the time of the COVID-19 pandemic, and what differences there are in their organization of religious life. In order to achieve the set goal, qualitative methods were implemented in the research. As part of the qualitative paradigm, in-depth individual interviews were used, involving individuals responsible for organizing religious life at the parish or congregation level. The interviewees were clergymen from the most important denominations, ranging from Catholic and Orthodox to broadly understood Protestant denominations. The paper contains a review of relevant literature. It presents the results and discussion of qualitative research, and it also indicates the research limitations. The study reveals that individual churches have limited (Catholic and Orthodox) or totally suspended (Protestants) their religious life in the actual community-based dimension. The decisions made by the clergymen, regardless of their personal views, resulted from the assumed ecclesiology and tradition. While changing the organization of religious life, the churches maintained contact with the believers in various ways, using modern technologies and access to public media in this regard. Although the churches are not changing their doctrinal positions, they declare different forms of cooperation.


title: Excess cases of influenza suggest an earlier start to the coronavirus epidemic in Spain than official figures tell us: an analysis of primary care electronic medical records from over 6 million people from Catalonia

text: Objectives: There is uncertainty about when the first cases of COVID-19 appeared in Spain, as asymptomatic patients can transmit the virus. We aimed to determine whether influenza diagnoses masked early COVID-19 cases and, if so, estimate numbers of undetected COVID-19 cases in a large database of primary-care records covering >6 million people in Catalonia. Design: Time-series study of influenza and COVID-19 cases, using all influenza seasons from autumn-winter 2010-2011 to autumn-winter 2019-2020. Setting: Primary care, Catalonia, Spain. Participants: People registered in one of the contributing primary-care practices, covering >6 million people and >85% of the population. Main outcome measures: Weekly new cases of influenza and COVID-19 diagnosed in primary care. Analyses: Daily counts of both cases were computed using the total cases recorded over the previous 7 days to avoid weekly effects on recording practice. Epidemic curves were characterised for the 2010-2011 to 2019-2020 influenza seasons. Influenza seasons with a similar epidemic curve and peak case number as the 2019-2020 season were used to model predictions for 2019-2020. ARIMA models were fitted to the included influenza seasons, overall and stratified by age, to estimate expected case numbers. Daily excess influenza cases were defined as the number of observed minus expected cases. Results: Four influenza season curves (2011-2012, 2012-2013, 2013-2014, and 2016-2017) were used to estimate the number of expected cases of influenza in 2019-2020. Between 4 February 2020 and 20 March 20202, 8,017 (95% CI: 1,841 to 14,718) excess influenza cases were identified. This excess was highest in the 15-64 age group. Conclusions: COVID-19 cases may have been present in the Catalan population when the first imported case was reported on 25 February 2020. COVID-19 carriers may have been misclassified as influenza diagnoses in primary care, boosting community transmission before public health measures were taken. In future, the surveillance of excess influenza cases using widely available primary-care electronic medical records could help detect new outbreaks of COVID-19 or other influenza-like illness-causing pathogens. Earlier detection would allow public health responses to be initiated earlier than during the current crisis.


Abnormal Hemostatic Parameters and Risk of Thromboembolism Among Patients With COVID-19 Infection


title: Potential biochemical markers to identify severe cases among COVID-19 patients

text: There is a high mortality and long hospitalization period for severe cases with 2019 novel coronavirus disease (COVID-19) pneumonia. Therefore, it makes sense to search for a potential biomarker that could rapidly and effectively identify severe cases early. Clinical samples from 28 cases of COVID-19 (8 severe cases, 20 mild cases) in Zunyi District from January 29, 2020 to February 21, 2020 were collected and otherwise statistically analysed for biochemical markers. Serum urea, creatinine (CREA) and cystatin C (CysC) concentrations in severe COVID-19 patients were significantly higher than those in mild COVID-19 patients (P<0.001), and there were also significant differences in serum direct bilirubin (DBIL), cholinesterase (CHE) and lactate dehydrogenase (LDH) concentrations between severe and mild COVID-19 patients (P<0.05). Serum urea, CREA, CysC, DBIL, CHE and LDH could be used to distinguish severe COVID-19 cases from mild COVID-19 cases. In particular, serum biomarkers, including urea, CREA, CysC, which reflect glomerular filtration function, may have some significance as potential indicators for the early diagnosis of severe COVID-19 and to distinguish it from mild COVID-19. Glomerular filtration function injury in severe COVID-19 patients should also be considered by clinicians.


title: Tail Risk of Contagious Diseases

text: Applying a modification of Extreme value Theory (thanks to a dual distribution technique by the authors on data over the past 2,500 years, we show that pandemics are extremely fat-tailed in terms of fatalities, with a marked potentially existential risk for humanity. Such a macro property should invite the use of Extreme Value Theory (EVT) rather than naive interpolations and expected averages for risk management purposes. An implication is that potential tail risk overrides conclusions on decisions derived from compartmental epidemiological models and similar approaches.


title: Perioperative airway management in patients infected with COVID-19/ Manejo de la vía aérea en el perioperatorio de los pacientes infectados con COVID-19

text: Coronavirus disease 2019 (COVID-19) is highly contagious. Transmission is predominantly by droplet spread. Procedures during the initial handling of the airway and critical areas can generate drops and aerosols that increase the risk of transmission. The aim of this paper is to review the recommendations and guidelines related to airway management in patient infected by SARS-Cov-2.


Erweiterte lebensrettende Maßnahmen bei Erwachsenen: COVID-19-Leitlinien des European Resuscitation Council


RAPID COMMUNICATION 22 March 2020 Estimating excess 1- year mortality from COVID-19 according to underlying conditions and age in England: a rapid analysis using NHS health records in 3.8 million adults Background: The medical, health service, societal and economic impact of the COVID-19 emergency has unknown effects on overall population mortality. Previous models of population mortality are based on death over days among infected people, nearly all of whom (to date at least) have underlying conditions. Models have not incorporated information on high risk conditions or their longer term background (pre-COVID-19) mortality. We estimated the excess number of deaths over 1 year under different COVID-19 incidence rates and differing mortality impacts. Methods: Using population based linked primary and secondary care electronic health records in England (HDR UK - CALIBER), we report the prevalence of underlying conditions defined by UK Public Health England COVID-19 guidelines (16 March 2020) in 3,862,012 individuals aged ≥30 years from 1997-2017. We used previously validated phenotypes, openly available (https://caliberresearch.org/portal), for each condition using ICD-10 diagnosis, Read, procedure and medication codes. We estimated the 1-year mortality in each condition, and developed simple models of excess COVID-19-related deaths assuming relative risk (RR) of the impact of the emergency (compared to background mortality) of 1.2, 1.5 and 2.0. Findings: 20.0% of the population are at risk according to current PHE guidelines, of which; 13.7% were age>70 years and 6.3% aged ≤70 years with ≥1 underlying condition (cardiovascular disease (2.3%), diabetes (2.2%), steroid therapy (1.9%), severe obesity (0.9%), chronic kidney disease (0.6%) and chronic obstructive pulmonary disease, COPD (0.5%). Multimorbidity (co-occurrence of ≥2 conditions in an individual) was common (10.1%). The 1-year mortality in the at-risk population was 4.46%, and age and underlying conditions combine to influence background risk, varying markedly across conditions (5.9% in age>70 years, 8.6% for COPD and 13.1% in those with ≥3 or more conditions). In a suppression scenario (at SARS CoV2 rates of 0.001% of the UK population), there would be minimal excess deaths (3 and 7 excess deaths at relative risk, RR, 1.5 and 2.0 respectively). At SARS CoV2 rates of 10% of the UK population (mitigation) the model estimates the numbers of excess deaths as: 13791, 34479 and 68957 (at RR 1.2, 1.5 and 2.0 respectively). At SARS CoV2 rates of 80% in the UK population (do-nothing), the model estimates the number of excess deaths as 110332, 275,830 and 551,659 (at RR 1.2, 1.5 and 2.0) respectively. Interpretation: We provide the public, researchers and policy makers a simple model to estimate the excess mortality over 1 year from COVID-19, based on underlying conditions at different ages. If the relative mortality impact of COVID-19 were to be about 20% (similar magnitude as the established winter vs summer mortality excess), then the excess deaths would be 0 when 1 in 100 000 (suppression), 13791 when 1 in 10 (mitigation) and 110332 when 8 in 10 are infected (do nothing) scenario. However, the relative impact of COVID-19 is unknown. If the emergency were to double the mortality risk, then we estimate 7, 68957 and 551,659 excess deaths in the same scenarios. These results may inform the need for more stringent suppression measures as well as efforts to target those at highest risk for a range of preventive interventions.


title: The global population of SARS-CoV-2 is composed of six major subtypes

text: The World Health Organization characterized the COVID-19 as a pandemic in March 2020, the second pandemic of the 21st century. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-stranded RNA betacoronavirus of the family Coronaviridae. Expanding virus populations, as that of SARS-CoV-2, accumulate a number of narrowly shared polymorphisms imposing a confounding effect on traditional clustering methods. In this context, approaches that reduce the complexity of the sequence space occupied by the SARS-CoV-2 population are necessary for a robust clustering. Here, we proposed the subdivision of the global SARS-CoV-2 population into sixteen well-defined subtypes by focusing on the widely shared polymorphisms in nonstructural (nsp3, nsp4, nsp6, nsp12, nsp13 and nsp14) cistrons, structural (spike and nucleocapsid) and accessory (ORF8) genes. Six virus subtypes were predominant in the population, but all sixteen showed amino acid replacements which might have phenotypic implications. We hypothesize that the virus subtypes detected in this study are records of the early stages of the SARS-CoV-2 diversification that were randomly sampled to compose the virus populations around the world, a typical founder effect. The genetic structure determined for the SARS-CoV-2 population provides substantial guidelines for maximizing the effectiveness of trials for testing the candidate vaccines or drugs.


title: COVID-19 pandemic: A Hill type mathematical model predicts the US death number and the reopening date

text: A mathematical model that can be used to estimate the total number of cases and deaths due to COVID-19 pandemic is presented in this study. The parameters and the associated uncertainty in the model are optimized and quantified using various reported data sets reported from different countries. The results suggest that, by the mid of June or early July 2020, the outbreak will strongly decay and the US will have about 800K confirmed cases and less than 50K deaths.


title: Systemic hypoferraemia and severity of hypoxaemic respiratory failure in COVID-19

text: Coronavirus disease 2019 (COVID-19) mortality is associated with hypoxaemia, multiorgan failure, and thromboinflammation. However severity of disease varies considerably and understanding physiological changes that may link to poor outcomes is important. Although increased serum ferritin has been observed in COVID-19 patients consistent with inflammation, other iron parameters have not been examined to our knowledge. Because iron is required for immunity and oxygen utilisation, and dysregulated iron homeostasis has been observed in COPD, we investigated serum iron concentrations in 30 patients with COVID-19 requiring ICU admission. All patients had low serum iron but patients with severe hypoxemic respiratory failure had more profound hypoferraemia. The area under the curve for receiver operating characteristic curves for serum iron to identify severe hypoxemia was 0.95; the optimal Youden Index for distinguishing between severe and non-severe hypoxemia was a serum iron concentration of 2.9 micromol/L. By linear regression, serum iron was associated with lymphocyte count and PaO2/FiO2. In conclusion, profound hypoferraemia identifies COVID-19 patients with severe hypoxaemia. Serum iron is a simple biomarker that could be usefully employed to stratify patients and monitor disease. Severe hypoferraemia may plausibly impair critical iron-dependent processes such as lymphocyte responses and hypoxia sensing, contributing to pathology, and is potentially treatable.


docid: qympygtp

title: State-level tracking of COVID-19 in the United States

text: As of 1st June 2020, the US Centers for Disease Control and Prevention reported 104,232 confirmed or probable COVID-19-related deaths in the US. This was more than twice the number of deaths reported in the next most severely impacted country. We jointly modelled the US epidemic at the state-level, using publicly available death data within a Bayesian hierarchical semi-mechanistic framework. For each state, we estimate the number of individuals that have been infected, the number of individuals that are currently infectious and the time-varying reproduction number (the average number of secondary infections caused by an infected person). We used changes in mobility to capture the impact that non-pharmaceutical interventions and other behaviour changes have on the rate of transmission of SARS-CoV-2. Nationally, we estimated 3.7% [3.4%-4.0%] of the population had been infected by 1st June 2020, with wide variation between states, and approximately 0.01% of the population was infectious. We also demonstrated that good model forecasts of deaths for the next 3 weeks with low error and good coverage of our credible intervals.


title: Metabolic disturbances and inflammatory dysfunction predict severity of coronavirus disease 2019 (COVID-19): a retrospective study

text: Background: The coronavirus disease 2019 (COVID-19) is spreading worldwide with 16,558 deaths till date. Serum albumin, high-density lipoprotein (HDL-C), and C-reactive protein have been known to be associated with the severity and mortality of community-acquired pneumonia. However, the characteristics and role of metabolic and inflammatory indicators in COVID-19 is unclear. Methods: We included 97 hospitalized patients with laboratory-confirmed COVID-19. Epidemiological, clinical, and laboratory indices; radiological features; and treatment were analysed. The differences in the clinical and laboratory parameters between mild and severe COVID-19 patients and the role of these indicators in severity prediction of COVID-19 were investigated. Results: All were Wuhan residents with contact with confirmed COVID-19 cases. The median age was 39 years (IQR: 30-59). The most common presenting symptoms were fever (58.8%), cough (55.7%), and fatigue (33%). Other features were lymphopenia, impaired fasting glucose, hypoproteinaemia, hypoalbuminemia, low high-density lipoproteinemia. Decrease in lymphocyte count, serum total protein, serum albumin, high-density lipoprotein cholesterol (HDL-C), ApoA1, CD3+T%, and CD8+T% were found to be valuable in predicting the transition of COVID-19 from mild to severe illness. Chest computed tomography (CT) images showed that the absorption of bilateral lung lesions synchronized with the recovery of metabolic and inflammatory indicators. Conclusions: Hypoproteinaemia, hypoalbuminemia, low high-density lipoproteinemia, and decreased ApoA1, CD3+T%, and CD8+T% could predict severity of COVID-19. Lymphocyte count, total serum protein, and HDL-C may be potentially useful for the evaluation of COVID-19.


title: The impact of goggle-associated harms to health and working status of nurses during management of COVID-19

text: Background To investigate the impact of goggles on their health and clinical practice during management of patients with COVID-19. Methods 231 nurse practitioners were enrolled who worked in isolation region in designated hospitals to admit patients with COVID-19 in China. Demographic data, goggle-associated symptoms and underlying reasons, incidence of medical errors or exposures, the effects of fog in goggles on practice were all collected. Data were stratified and analyzed by age or working experience. Risk factors of goggle-associated medical errors were analyzed by multivariable logistical regression analysis. Findings Goggle-associated symptoms and foggy goggles widely presented in nurses. The most common symptoms were headache, skin pressure injury and dizziness. Headache, vomit and nausea were significantly fewer reported in nurses with longer working experience while rash occurred higher in this group. The underlying reasons included tightness of goggles, unsuitable design and uncomfortable materials. The working status of nurses with more working experience was less impacted by goggles. 11.3% nurses occurred medical exposures in clinical practice while 19.5% nurses made medical errors on patients. The risk factors for medical errors were time interval before adapting to goggle-associated discomforts, adjusting goggles and headache. Interpretation Goggle-associated symptoms and fog can highly impact the working status and contribute to medical errors during management of COVID-19. Increased the experience with working in PPE through adequate training and psychological education may benefit for relieving some symptoms and improving working status. Improvement of goggle design during productive process was strongly suggested to reduce incidence of discomforts and medical errors.


title: Lung Bronchial Epithelial Cells are HIV Targets for Proviral Genomic Integration

text: In the era of highly active anti-retroviral therapy (HAART), obstructive lung diseases (OLDs) are common among the people living with HIV (PLWH); however, the mechanism by which HIV induces OLDs is unclear. Although human bronchial epithelial cells (HBECs) express HIV coreceptors and are critical in regulating lung immune responses, their role in transmitting HIV remains unclear. Herein, we present evidence that HIV-1 infects normal HBECs and the viral DNA is integrated in the genome to establish the viral latency. To prove that HIV productively infects HBECs, we demonstrate: (a) along with CXCR4, HBECs express the HIV-receptor CD4, and are induced to express CCR5 by IL-13 treatment; (b) following infection with HIV, HBECs produce HIV-p24 and contain the latent HIV provirus, which is activated by endotoxin and/or vorinostat; (c) DNA from HIV-1 infected HBECs contains the HIV-specific gag and nef genes, along with Alu sequences, confirming the integration of HIV in the host DNA; (d) the lung epithelial cells of HIV-infected subjects and SHIV-infected cynomolgus macaques are positive for HIV-specific transcripts. Thus, these studies suggest that HIV establishes latency in lung epithelial cells, making them potential HIV reservoirs. The long-living lung epithelial cells, activated by commonly encountered lung infections, might represent an ideal HIV target/reservoir, contributing to OLDs and other HIV-associated lung comorbidities.


COVID-19 and vascular medicine/ Covid-19 et médecine vasculaire


docid: jjdtuofy

title: Spread of SARS-CoV-2 Coronavirus likely to be constrained by climate

text: As new cases of COVID-19 are being confirmed pressure is mounting to increase understanding of the factors underlying the spread the disease. Using data on local transmissions until the 23rd of March 2020, we develop an ensemble of 200 ecological niche models to project monthly variation in climate suitability for spread of SARS-CoV-2 throughout a typical climatological year. Although cases of COVID-19 are reported all over the world, most outbreaks display a pattern of clustering in relatively cool and dry areas. The predecessor SARS-CoV-1 was linked to similar climate conditions. Should the spread of SARS CoV-2 continue to follow current trends, asynchronous seasonal global outbreaks could be expected. According to the models, temperate warm and cold climates are more favorable to spread of the virus, whereas arid and tropical climates are less favorable. However, model uncertainties are still high across much of sub- Saharan Africa, Latin America and South East Asia. While models of epidemic spread utilize human demography and mobility as predictors, climate can also help constrain the virus. This is because the environment can mediate human-to-human transmission of SARS-CoV-2, and unsuitable climates can cause the virus to destabilize quickly, hence reducing its capacity to become epidemic.


title: Scaling diagnostics in times of COVID-19: Rapid prototyping of 3D-printed water circulators for Loop-mediated Isothermal Amplification (LAMP) and detection of SARS-CoV-2 virus

text: By the first week of April 2020, more than 1,500,000 positive cases of COVID-19 and more than 50,000 deaths had been officially reported worldwide. While developed countries such as the USA, Italy, England, France, Spain, and Germany struggle to mitigate the propagation of SARS-CoV-2, the COVID-19 pandemic arrived in Latin America, India, and Africa -territories in which the mounted infrastructure for diagnosis is greatly underdeveloped. An actual epidemic emergency does not provide the required timeframe for testing new diagnostic strategies; therefore, the first line of response must be based on commercially and readily available resources. Here, we demonstrate the combined use of a three-dimensional (3D)-printed incubation chamber for commercial Eppendorf PCR tubes, and a colorimetric embodiment of a loop-mediated isothermal amplification (LAMP) reaction scheme for the detection of SARS-CoV-2 nucleic acids. We used this strategy to detect and amplify SARS-CoV-2 DNA sequences using a set of in-house designed initiators that target regions encoding the N protein. We were able to detect and amplify SARS-CoV-2 nucleic acids in the range of ~625 to 2 X 105 DNA copies by this straightforward method. The accuracy and simplicity of this diagnostics strategy may provide a cost-efficient and reliable alternative for use during the COVID-19 pandemics, particularly in underdeveloped regions were the availability of RT-qPCR instruments may be limited. Moreover, the portability, ease of use, and reproducibility of this strategy make it a reliable alternative for deployment of point-of-care SARS-CoV-2 detection efforts during the pandemics.


title: Coronaviruserkrankung 2019 (COVID-19) und Schwangerschaft: Übersicht und Bericht des ersten deutschen Falls mit COVID-19 bei Gestationsdiabetes

text: Since the beginning of the coronavirus pandemic with SARS-CoV‑2 (severe acute respiratory syndrome coronavirus 2) in January 2020, more than 100 cases of pregnant Chinese women have been published, including individuals with gestational diabetes (GDM). The descriptive overview reports on the clinical presentation of COVID-19 as well as on obstetric and neonatal outcome data. The main symptoms of the overall milder course of infection are fever, cough and dyspnea. So far, there is no evidence of intrauterine transmission of the virus and no evidence of breast milk transfer. Postnatal infections of infants of infected mothers are documented, but the course is usually mild. The available data are informative for preparing health professionals for the expected infections in pregnant women with the comorbidity diabetes mellitus.


docid: ablounoq

title: Developing optimal policies to fight pandemics and covid-19 combat in the United States

text: The world has faced many outbreaks and pandemics with hundreds of millions of deaths throughout its history. Those epidemics are global health concerns and as well as serious economic issues. There is certain need to allocate scarce sources efficiently to fight such epidemics in both personal and global dimensions. Here we develop and propose two optimization models to maximize the total protection from any epidemic, pandemic or bioterror attacks; the first one is personal protection model or protocol and the other one is mass protection model that is inspired by the well-known weapon-target assignment problem of operations research. These efforts are optimal allocation of scarce medical and economic resources to save millions of lives- gift of life. We implement our general mathematical programming models with real-world data to fight the coronavirus pandemic for a person and the United States. Our personal protection protocol provides 99.99% protection from COVID-19 for an American through personal strategies when the mass protection model supplies 96.961% protection on average from coronavirus pandemic for the United States through countrywide policies. The mass protection model which recommends general policy frame for health care policy makers could be applied for any epidemic at any level from county to city, to state and country as well as in global scale. The mathematical relation between the personal protection protocol and the mass protection model also highlights the fact of unus pro omnibus, omnes pro uno (one for all, all for one) for fighting epidemics- particularly the moving enemy, novel coronavirus which is double invisible due to its viral nature and the availability of the high level of asymptomatic cases. Recognize the enemy, as protecting yourself means protecting people, love life, follow the rules and stay at home. That is the greatest ever social impact.


title: A rapid review of available evidence on the serial interval and generation time of COVID-19

text: Abstract: Background: The serial interval is the time between symptom onsets in an infector infectee pair. The generation time, also known as the generation interval, is the time between infection events in an infector infectee pair. The serial interval and the generation time are key parameters for assessing the dynamics of a disease. A number of scientific papers reported information pertaining to the serial interval and/or generation time for COVID19. Objectives: Conduct a rapid review of available evidence to advise on appropriate parameter values for serial interval and generation time in national COVID19 transmission models for Ireland and on methodological issues relating to those parameters. Methods: A review of scientific literature was conducted covering the period between December 1, 2019 and April 27, 2020. Nineteen scientific papers were evaluated in detail from 27 papers that contained information on the serial interval and/or generation time for COVID19. Results: The mean of the serial interval ranged from 3.1 to 7.5 days, based on 22 estimates, and the median from 1.9 to 6.0 days (based on 7 estimates). Only three estimates were provided for the mean of the generation time. These ranged from 3.9 to 5.2 days. One estimate of 5.0 days was provided for the median of the generation time. Discussion: The values of the estimates for serial interval and generation time are heavily influenced by the contact rates between infectious and susceptible individuals. Mitigation measures that are introduced in a country or region are of paramount importance in this regard. The serial interval estimate of 6.6 days (95% confidence interval: 0.7, 19.0) from the paper by Cereda et al.[10] is likely to be the most relevant to European countries. National estimates should be obtained as soon as possible.


title: Artificial intelligence systems aim to sniff out signs of COVID-19 outbreaks

text: The international alarm about the COVID-19 pandemic was sounded first not by a human, but by a computer HealthMap, a website run by Boston Children’s Hospital, uses artificial intelligence (AI) to scan social media, news reports, internet search queries, and other information streams for signs of disease outbreaks On 30 December 2019, the data-mining program spotted a news report of a new type of pneumonia in Wuhan, China The one-line email bulletin noted that seven people were in critical condition and rated the urgency at three on a scale of five


title: Antiviral Theatrics?

text: This, though, is an official organ of the Chinese state – none more so – showing all sorts of white-fog-spraying devices being deployed outdoors, with the caption “Full-front disinfection work has started in #Wuhan, an effort to contain the spread of #coronavirus“ Maybe there’s something in the mix that someone thinks will do some good against coronavirus particles – I doubt if they’re correct, if so – or maybe the whole thing is just meant to show that the Authorities Are Doing Something


docid: jyktuvyy

title: How Should Clinicians Interpret Imprecise Trials Assessing Drugs for COVID-19 Patients?

text: As the COVID-19 pandemic progresses, researchers are reporting findings of randomized trials comparing standard care with care augmented by experimental drugs. The trials have small sample sizes, so estimates of treatment effects are imprecise. Seeing imprecision, clinicians reading research articles may find it difficult to decide when to treat patients with experimental drugs. Whatever decision criterion one uses, there is always some probability that random variation in trial outcomes will lead to prescribing sub-optimal treatments. A conventional practice when comparing standard care and an innovation is to choose the innovation only if the estimated treatment effect is positive and statistically significant. This practice defers to standard care as the status quo. We argue that clinicians should ignore conventional measures of statistical significance. They should choose treatments that work best in trials, taking side effects into account and recognizing that treatment effects may vary with patient risk factors. To evaluate treatments, we use the concept of near optimality, which jointly considers the probability and magnitude of decision errors. An appealing decision criterion from this perspective is the empirical success rule, which chooses the treatment with the highest observed average patient outcome in the trial. Considering the design of COVID-19 trials, we show that the empirical success rule yields treatment results that are much closer to optimal than those generated by prevailing decision criteria based on hypothesis tests.


title: Time-Resolving the COVID-19 Outbreak using frequency domain analysis

text: Difficulties assessing and predicting the current outbreak of the severe acute respiratory syndrome coronavirus 2 can be traced, in part, to the limitations of a static description of a dynamic system. Fourier transforming the time-domain data of infections and fatalities into the frequency domain makes the dynamics easily accessible. Defining a quantity like the case fatality as a spectral density allows a more sensible comparison between different countries and demographics during an ongoing outbreak. Such a case fatality informs not only how many of the confirmed cases end up as fatalities, but also when. For COVID-19, knowing this time and using the entire case fatality spectrum allows determining that an outbreak had entered a steady-state (most likely its end) about 14 days before this is obvious from time-domain data. The lag between confirmations and deaths also helps to estimate the effectiveness of contact management: The larger the lag, the less time the average confirmed person had to infect people before quarantine.


title: Research opportunities for a more resilient post-COVID-19 supply chain – closing the gap between research findings and industry practice

text: Purpose: The COVID-19 crisis has caused major supply chain disruptions, and these can be traced back to basic supply chain risks that have previously been well identified in literature. The purpose of this paper is to suggest a pathway for closing the gap between supply chain resilience research and efforts in industry to develop a more resilient supply chain. Design/methodology/approach: Based upon virtual roundtables with supply chain executives, supplemented with interviews and publicly available datapoints about COVID-19 impact on the supply chain, we explore challenges in industry and suggest opportunity areas where research can support efforts in industry to improve supply chain resilience. Findings: During the COVID-19 crisis, participating supply chain executives are experiencing textbook supply, demand and control risks in the supply chain. They also observe a lack of preparedness, shortcomings of current response plans and the need for greater supply chain resilience. Focus areas in improving resilience mirror generic recommendations from literature and provide a rich opportunity to reduce the gap between research findings and efforts in industry. Research limitations/implications: More empirical, event-based and less conceptual research into supply chain resilience has been called for several times during the last two decades. COVID-19 provides a very rich opportunity for researchers to conduct the type of research that has been called for. This research may contribute to the structurally de-risking of supply chains. Areas of research opportunity include decision models for supply chain design that avoid overfocusing on costs only, and that consider the value of flexibility, short response times and multiple sources as well as methods for enriching supplier segmentation and evaluation models to reduce a focus on savings and payment terms only. Practical implications: Key levers for de-risking the supply chain include the need to balance global sourcing with nearshore and local sourcing, the adoption of multiple sources and a greater utilization of information technology to drive more complete and immediate information availability. Perhaps most importantly, talent management in supply chain management needs to promote a focus not just on costs, but also on resilience as well as on learning from current events to improve decision-making. Social implications: There is a great opportunity for supply chain managers to grow their contribution to society beyond risk response into the proactive reduction of risks for the future. Researchers can serve society by informing this progress with impactful research. Originality/value: This article offers initial empirical exploration of supply chain risks experienced in the context of COVID-19 and approaches considered in industry to improve supply chain resilience. Opportunities for empirical, event-based and less conceptual research that has been called for years, are identified. This research can help close the gap between supply chain resilience research and efforts in industry to improve supply chain resilience. Hopefully the research opportunities identified can inspire the flurry of research that can be expected in response to the multiple special issues planned by journals in our field.


title: Assessing the effect of global travel and contact reductions to mitigate the COVID-19 pandemic and resurgence

text: Travel and physical distancing interventions have been implemented across the World to mitigate the COVID-19 pandemic, but studies are needed to quantify the effectiveness of these measures across regions and time. Timely population mobility data were obtained to measure travel and contact reductions in 135 countries or territories. During the 10 weeks of March 22 - May 30, 2020, domestic travel in study regions has dramatically reduced to a median of 59% (interquartile range [IQR] 43% - 73%) of normal levels seen before the outbreak, with international travel down to 26% (IQR 12% - 35%). If these travel and physical distancing interventions had not been deployed across the World, the cumulative number of cases might have shown a 97-fold (IQR 79 - 116) increase, as of May 31, 2020. However, effectiveness differed by the duration and intensity of interventions and relaxation scenarios, with variations in case severity seen across populations, regions, and seasons.


title: COVID-19: La nueva pandemia con muchas lecciones y nuevos retos. Revisión Narrativa/ COVID-19: The new pandemic with many lessons and new challenges. Narrative Review

text: El nuevo coronavirus (2019-nCoV, SARS-CoV-2 o COVID-19) que hasta el momento ha afectado a más de 180 países de casi todos los continentes, fue declarado por la Organización Mundial de la Salud como pandemia por su alcance mundial y hasta la fecha, ha sobrepasado el millón de casos de infectados, de los cuales el 5,54% han sido letales. La emergencia de esta enfermedad, se ha explicado por el surgimiento de un coronavirus humano desconocido con incrementados factores de virulencia. El número exponencialmente creciente de casos en el mundo, refleja en parte la rápida transmisión del COVID-19, que se traduce en una dura prueba para los sistemas de salud de los países más afectados. Los retos que ha representado esta pandemia, muchos han tenido sus bases en las lecciones aprendidas de la pandemia de SARS en 2003 y dado el parecido genómico de esta nueva cepa de coronavirus, ha sido designado como SARS-CoV-2. No obstante, los parecidos, hay muchas preguntas aun por responder, especialmente en lo que respecta a los mecanismos de transmisión. Contar con datos detallados y precisos permitirá comprender y hacer un seguimiento del alcance de esta pandemia y fortalecer los esfuerzos de prevención y respuesta, en virtud que hasta el momento los tratamientos son experimentales y la vacuna podría estar disponible a mediano o largo plazo.


title: Distortion Prediction and NURBS Based Geometry Compensation for Reducing Part Errors in Additive Manufacturing

text: Abstract Additive Manufacturing (AM) is a process in which a part is typically fabricated by depositing materials layer by layer. Powder Bed Fusion Additive Manufacturing Process (PBFAM) is one type of AM process which utilizes a high energy laser source to heat and fuse metal powders into a solid part. The constant cycle of heating and cooling in each layer causes thermal deformation associated with residual stresses that reduce the geometric accuracy of the build. To remedy this problem, a compensation algorithm is presented in this paper which modifies the native NURBS CAD geometry of the part to counteract the thermal distortion. An inherent strain-based fast distortion prediction model is used to predict the thermal distortion of the part. The resulting distorted FEA nodes are used to construct a NURBS based compensated geometry using nonlinear least square fitting approach using the original NURBS parameters. Compensating the native NURBS geometry of the model provides more accuracy for the part build rather than compensating STL models. Validation of the algorithm is performed using two case studies by comparing the thermal deformation of pre and post compensated NURBS geometries. The accuracy and robustness of the algorithm for achieving geometric tolerances are further assessed by comparing the flatness and cylindricity tolerances values of the part feature from the two case studies.


title: Quantifying the impact of US state non-pharmaceutical interventions on COVID-19 transmission

text: COVID-19 is an ongoing public health emergency. Without a vaccine or effective antivirals, non-pharmaceutical interventions form the foundation of current response efforts. Quantifying the efficacy of these interventions is crucial. Using mortality data and a classification guide of state level responses, we relate the intensity of interventions to statistical estimates of transmission, finding that more stringent control measures are associated with larger reductions in disease proliferation. Additionally, we observe that transmission increases with population density, but not population size. These results may help inform future response efforts.


title: Clinical diagnosis of 8274 samples with 2019-novel coronavirus in Wuhan

text: Background: 2019-Novel coronavirus (2019-nCoV) outbreaks create challenges for hospital laboratories because thousands of samples must be evaluated each day. Sample types, interpretation methods, and corresponding laboratory standards must be established. The possibility of other infections should be assessed to provide a basis for clinical classification, isolation, and treatment. Accordingly, in the present study, we evaluated the testing methods for 2019-nCoV and co-infections. Methods: We used a fluorescence-based quantitative PCR kit urgently distributed by the Chinese CDC to detect 8274 close contacts in the Wuhan region against two loci on the 2019-nCoV genome. We also analyzed 613 patients with fever who underwent multiple tests for 13 respiratory pathogens; 316 subjects were also tested for 2019-nCoV. Findings: Among the 8274 subjects, 2745 (33.2%) had 2019-nCoV infection; 5277 (63.8%) subjects showed negative results in the 2019-nCoV nucleic acid test (non-019-nCoV); and 252 cases (3.0%) because only one target was positive, the diagnosis was not definitive. Sixteen patients who originally had only one positive target were re-examined a few days later; 14 patients (87.5%) were finally defined as 2019-nCoV-positive, and 2 (12.5%) were finally defined as negative. The positive rates of nCoV-NP and nCovORF1ab were 34.7% and 34.7%, respectively. nCoV-NP-positive only and nCovORF1ab-positive cases accounted for 1.5% and 1.5%, respectively. In the 316 patients with multiple respiratory pathogens, 104 were positive for 2019-nCov and 6/104 had co-infection with coronavirus (3/104), influenza A virus (2/104), rhinovirus (2/104), and influenza A H3N2 (1/104); the remaining 212 patients had influenza A virus (11/202), influenza A H3N2 (11/202), rhinovirus (10/202), respiratory syncytial virus (7/202), influenza B virus (6/202), metapneumovirus (4/202), and coronavirus (2/202). Interpretation: Clinical testing methods for 2019-nCoV require improvement. Importantly, 5.8% of 2019-nCoV infected and 18.4% of non-2019-nCoV-infected patients had other pathogen infections. It is important to treat combined infections and perform rapid screening to avoid cross-contamination of patients. A test that quickly and simultaneously screens as many pathogens as possible is needed.


title: Infection Groups Differential (IGD) Score Reveals Infection Ability Difference between SARS-CoV-2 and Other Coronaviruses

text: The Corona Virus Disease 2019 (COVID-19) pandemic that began in late December 2019 has resulted in millions of cases diagnosed worldwide. Reports have shown that SARS-CoV-2 shows extremely higher infection rates than other coronaviruses. This study conducted a phylogenetics analysis of 91 representative coronaviruses and found that the functional spike protein of SARS-CoV-2, which interacts with the human receptor ACE2, is actually not undergoing distinct selection pressure compared to other coronaviruses. Furthermore, we define a new measurement, infection group differential (IGD) score, in assessing the infection ability of two human coronavirus groups. There are nine extremely high IGD (ehIGD) sites in the receptor-binding domain (RBD) out of 40 high IGD (hIGD) sites that exhibit a unique infection-related pattern from the haplotype network and docking energy comparison. These 40 hIGD sites are basically conserved among the SARS-CoV-2, i.e. there are only two hIGD sites mutated in four out of 1,058 samples, defined as rare-mutation hIGD (rhIGD) sites. In conclusion, ehIGD and rhIGD sites might be of great significance to the development of vaccines.


title: Immunoglobulin fragment F(ab’)2 against RBD potently neutralizes SARS-CoV-2 in vitro

text: COVID-19 caused by the emerging human coronavirus, SARS-CoV-2, has become a global pandemic, leading a serious threat to human health. So far, there is none vaccines or specific antiviral drugs approved for that. Therapeutic antibodies for SARS-CoV-2, was obtained from hyper immune equine plasma in this study. Herein, SARS-CoV-2 RBD with gram level were obtained through Chinese hamster ovary cells high-density fermentation. The binding of RBD to SARS-CoV-2 receptor, human ACE2, was verified and the efficacy of RBD in vivo was tested on mice and then on horses. As a result, RBD triggered high-titer neutralizing antibodies in vivo, and immunoglobulin fragment F(ab’)2 was prepared from horse antisera through removing Fc. Neutralization test demonstrated that RBD-specific F(ab’)2 inhibited SARS-CoV-2 with EC50 at 0.07 μg/ml, showing a potent inhibitory effect on SARS-CoV-2. These results highlights as RBD-specific F(ab’)2 as therapeutic candidate for SARS-CoV-2.


title: Relationship between Average Daily Temperature and Average Cumulative Daily Rate of Confirmed Cases of COVID-19

text: The rapid outbreak of the new Coronavirus (COVID-19) pandemic and the spread of the virus worldwide, especially in the Northern Hemisphere, have prompted various investigations about the impact of environmental factors on the rate of development of this epidemic. Different studies have called the attention to various parameters that may have influenced the spread of the virus, and in particular, the impact of climatic parameters has been emphasized. The main purpose of this study is to investigate the correlation between the average daily temperature and the rate of coronavirus epidemic growth in the infected regions. The main hypothesis object of our research is that between regions exhibiting a significant difference in the mean daily temperature, a significant difference is also observed in the average cumulative daily rate of confirmed cases, and that this does not happen if there is no significant difference in mean daily temperature. To test this research hypothesis, we carried on the case study of three regions in each of five countries and analyzed the correlation through F-test, and Independent-Samples T-Test. In all five selected countries, we found that when there is a significant difference in the daily mean temperature between two regions of a country, a significant difference exists also in the average cumulative daily rate of confirmed cases. Conversely, if there are no significant differences in the mean daily temperature of two regions in the same country, no significant difference is observed in the average cumulative daily rate of confirmed cases for these regions.


title: Clinical utility of targeted SARS-CoV-2 serology testing to aid the diagnosis and management of suspected missed, late or post-COVID-19 infection syndromes: results from a pilot service

text: Objectives: Determine indications and clinical utility of SARS-CoV-2 serology testing in adults and children. Design: Prospective evaluation of initial three weeks of a daily Monday to Friday pilot SARS-CoV-2 serology service for patients. Setting: Early post 'first-wave' SARS-CoV-2 transmission period at single centre London teaching hospital that provides care to the local community, as well as regional and national referral pathways for specialist services. Participants: 110 (72 adults, 38 children, age range 0-83 years, 52.7% female (n=58)). Interventions: Patient serum from vetted referrals tested on CE marked and internally validated lateral flow immunoassay (LFIA) (SureScreen Diagnostics) detecting antibodies to SARS-CoV-2 spike proteins, with result and clinical interpretation provided to the direct care team. Main outcome measures: Performance characteristics, source and nature of referrals, feasibility and clinical utility of the service, particularly the benefit for clinical decision-making. Results: The LFIA was deemed suitable for clinical advice and decision making following evaluation with 310 serum samples from SARS-CoV-2 PCR positive patients and 300 pre-pandemic samples, giving a sensitivity and specificity of 96.1% and 99.3% respectively. For the pilot, 115 referrals were received leading to 113 tests performed on 108 participants (sample not available for two participants); paediatrics (n=35), medicine (n=69), surgery (n=2) and general practice (n=2). 43.4% participants (n=49) had detectable antibodies to SARS-CoV-2. There were three main indications for serology; new acute presentations potentially triggered by recent COVID-19 infection e.g. PIMS-TS (n=26) and pulmonary embolism (n=5), potential missed diagnoses in context of a recent compatible illness (n=40), and making infection control and immunosuppression treatment decisions in persistently SARS-CoV-2 RNA PCR positive individuals (n=6). Conclusions: This study shows acceptable performance characteristics, feasibility and clinical utility of a SARS-CoV-2 serology service using a rapid, inexpensive and portable assay for adults and children presenting with a range of clinical indications. Results correlated closely with a confirmatory in-house ELISA. The study showed the benefit of introducing a serology service where there is a reasonable pre-test probability, and the result can be linked with clinical advice or intervention. Experience thus far is that the volume of requests from hospital referral routes are manageable within existing clinical and laboratory services; however, the demand from community referrals has not yet been assessed. Given recent evidence for a rapid decline in antibodies, particularly following mild infection, there is likely a limited window of opportunity to realise the benefit of serology testing for individuals infected during the 'first-wave' before they potentially fall below a measurable threshold. Rapidly expanding availability of serology services for NHS patients will also help understand the long-term implications of serostatus and prior infection in different patient groups, particularly before emergence of any 'second-wave' outbreak or introduction of a vaccination programme.


title: Insight into vaccine development for Alpha-coronaviruses based on structural and immunological analyses of spike proteins

text: Coronaviruses that infect humans belong to the Alpha-coronavirus (including HCoV-229E) and Beta-coronavirus (including SARS-CoV and SARS-CoV-2) genera. In particular, SARS-CoV-2 is currently a major threat to public health worldwide. However, no commercial vaccines against the coronaviruses that can infect humans are available. The spike (S) homotrimers bind to their receptors through the receptor-binding domain (RBD), which is believed to be a major target to block viral entry. In this study, we selected Alpha-coronavirus (HCoV-229E) and Beta-coronavirus (SARS-CoV and SARS-CoV-2) as models. Their RBDs were observed to adopt two different conformational states (lying or standing). Then, structural and immunological analyses were used to explore differences in the immune response with RBDs among these coronaviruses. Our results showed that more RBD-specific antibodies were induced by the S trimer with the RBD in the “standing” state (SARS-CoV and SARS-CoV-2) than the S trimer with the RBD in the “lying” state (HCoV-229E), and the affinity between the RBD-specific antibodies and S trimer was also higher in the SARS-CoV and SARS-CoV-2. In addition, we found that the ability of the HCoV-229E RBD to induce neutralizing antibodies was much lower and the intact and stable S1 subunit was essential for producing efficient neutralizing antibodies against HCoV-229E. Importantly, our results reveal different vaccine strategies for coronaviruses, and S-trimer is better than RBD as a target for vaccine development in Alpha-coronavirus. Our findings will provide important implications for future development of coronavirus vaccines. Importance Outbreak of coronaviruses, especially SARS-CoV-2, poses a serious threat to global public health. Development of vaccines to prevent the coronaviruses that can infect humans has always been a top priority. Coronavirus spike (S) protein is considered as a major target for vaccine development. Currently, structural studies have shown that Alpha-coronavirus (HCoV-229E) and Beta-coronavirus (SARS-CoV and SARS-CoV-2) RBDs are in lying and standing state, respectively. Here, we tested the ability of S-trimer and RBD to induce neutralizing antibodies among these coronaviruses. Our results showed that Beta-CoVs RBDs are in a standing state, and their S proteins can induce more neutralizing antibodies targeting RBD. However, HCoV-229E RBD is in a lying state, and its S protein induces a low level of neutralizing antibody targeting RBD. Our results indicate that Alpha-coronavirus is more conducive to escape host immune recognition, and also provide novel ideas for the development of vaccines targeting S protein.


title: How the COVID-19 pandemic is affecting paediatric orthopaedics practice: a preliminary report

text: PURPOSE: Since the state of alarm was decreed in Spain on 14 March 2020, the coronavirus disease 2019 (COVID-19) pandemic has had an extraordinary impact in paediatric hospitals. This study shows the effect of the pandemic on our practice in paediatric orthopaedics in a referral third level paediatric hospital. METHODS: We performed a single-centre retrospective review of the official census from a third level paediatric hospital from 14 March to 14 April for the years 2018, 2019 and 2020. RESULTS: The patients seen in our clinic during this period in 2020 decreased in by 82% (p < 0.001) compared with 2018 and 2019, however, the number of telemedicine consultations increased by 90.21% (p < 0.001). The total number of patients attending the clinic (including onsite and virtual) was reduced by 54.25% (p < 0.001). The total surgeries performed plummeted by 81% in this period in 2020 (p < 0.001) due to a reduction in elective cases of 94.6% (p < 0.001). No significant decrease was found in the number of urgent surgical cases per day in 2020 (p = 0.34). Finally, the number of orthopaedic patients admitted to our emergency department dropped by 78.6% during the state of alarm (p < 0.001). CONCLUSION: According to our results, the pandemic has significantly affected our daily practice by decreasing elective surgeries and onsite clinics, but other activities have increased. As we have implemented telemedicine and new technologies to adapt to this setback, we should take advantage of the situation to change our practice in the future to better allocate our health resources and to anticipate outbreaks. Published without peer review. LEVEL OF EVIDENCE: IV


title: Epidemic Situation and Forecasting of COVID-19 in Saudi Arabia using the SIR model

text: Background: Saudi Arabia is one of the countries affected by COVID-19 pandemic. This will lead to negative impacts in many sectors. Saudi Arabia not only plays an important role on the economical side because it is the leading country in oil production, but also because it is considered the heart of the Islamic countries. Although protective measures have been implemented in Saudi Arabia, the number of COVID-19 cases has increased. Aims of the study: This study aimed to employ SIR model to forecast the peak of COVID-19 progression and an estimation of it is end in Saudi Arabia. Method: Based on the World Health Organization data on COVID-19 progression in Saudi Arabia from March 3rd to April 29th, 2020, we reliably estimate the constant parameters and make predictions on the inflection point and potential ending time. Susceptible, Infected, and Recovered are the main components of the SIR model that were used to run the analysis. Result: The data showed an interesting result about the peak of the disease progression. It is projected to occur around the 20th day after running the model. According to the model, the peak time will be around the 20th of May. Then the cases will decrease until the 55th day, which is around June 20th. Conclusion: The result predicts a second peak and an estimation end of COVID-19 in Saudi Arabia. This data can inform the policy makers, who should try to contain the virus, to be prepared for what is coming next.


title: Cancer care in the time of COVID-19—a perspective from Pakistan

text: Across much of the world, cancer care has been sidelined to a variable degree by the global effort against the coronavirus pandemic. This paper discusses the impact of coronavirus infection on cancer diagnosis and treatment in two leading cancer centres in Pakistan. It also describes the effect that preparations for the expected surge in cases in Pakistan over the next few weeks have had on cancer care. There is an urgent need to evaluate the effect of delays in diagnosis and treatment on cancer stage and treatment, and to decide how to minimise these during likely future cycles of lockdown over the coming months and years.


title: An Ounce of Prevention: Coronavirus (COVID-19) and Mass Gatherings

text: Widespread, non-stop, and often sensational coverage of the coronavirus (COVID-19) has caught many governments flat-footed in efforts to protect the health and safety of their citizens. In response to the current global health event, the World Health Organization (WHO) declared COVID-19 a pandemic. Mass gatherings present a historic challenge in protecting the health and safety of attendees. The majority of the prominent mass gatherings are religious in nature. Global sporting events, such as the Olympics and the World Cup, pose unique health risks to attendees and host nations. Deferment or cancellation of such mass gatherings may exert an extraordinary economic loss to the host nation. Universal adoption of best practices for infection control is the surest way for governments to prepare for mass gatherings. In these uncertain times, it is up to intergovernmental organizations to be the voice of reason.


title: Estimating the parameters of SIR model of COVID-19 cases in India during lock down periods

text: From the pandemic scenario of COVID-19 disease cases in all over the world, the outbreak prediction becomes very complex for the emerging scientifically research. Several epidemiological mathematical models of spread are increasing day by day to forecast correctly. Here, the classical SIR modelling approach is carried out to study the different parameters of this model in case of India county. This type of approach analyzed by considering different governmental lock down measures in India. There are some assumptions were taken into account for fitting the model in Python simulation in each lock down scenario. The predicted parameters of SIR model showed some improvement in each case of lock down in India. The outcome results showed the extreme interventions should be taken to tackle this type of pandemic situation in near future.


Love and social distancing in the time of Covid-19: The philosophy and literature of pandemics


title: Structural Barriers to Green and Blue Spaces: A Scoping Review Protocol

text: Background Emerging evidence has demonstrated that nature-based interventions (NBIs) can improve mental and physical health. Considering that the global burden of poor mental health continues to rise, such interventions could be a cost-effective means to improve mental health, as well as reconnect individuals with the natural world, and thus aid efforts. However, the effectiveness of NBIs as a prescriptive intervention is, in part, a function of access to blue and green spaces. Accordingly, this scoping review will explore how structural inequalities influence the effectiveness of nature-based interventions as treatment options for mental and physical ill health. Methods A scoping review will be conducted to identify the barriers and facilitators associated with the utilisation of green and blue spaces. The review will follow the PRISMA-ScR guidelines, in addition to the associated Cochrane guidelines for scoping reviews. A literature search will be performed across five databases, and articles will be selected based on key inclusion/ exclusion criteria. All data will be extracted to a pre-defined charting table. The primary and secondary outcomes will be mental and physical health respectively. Discussion This review will better inform relevant stakeholders of the potential enablers and barriers of nature-based interventions, and thereby improve provision and implementation of NBIs as public health initiatives.


title: Low-delay Admittance Control of Hydraulic Series Elastic Actuator for Safe Human-Robot Collaboration

text: Abstract Current industrial manufacturing standards highlight safe human-robot collaboration. Therefore, compliance solutions, whether passive or active, are necessary. In this regard, series elastic actuators (SEAs) have attracted extensive interest for applications in industrial robotics owing to the low output impedance of these actuators, which can enhance interaction safety. Although considerable efforts have been expended to improve the control accuracy of SEAs, the time delay in impedance/admittance control has remained an unexplored problem. The use of filters in conventional methods can result in large time delay and considerable amplitude errors that degrade the performance and increase the risk of injury. This study resolves this problem by developing a method for low-delay admittance control of hydraulic SEAs. An external force observer (EFO)-based admittance scheme is first formulated. Thereafter, adaptive time series (ATS) compensators are introduced to improve position control and EFO. Based on the improved position controller and the ATS-based EFO (ATS-EFO), a novel low-delay admittance control scheme is developed. The proposed method only uses the load mass and spring stiffness information, thereby facilitating its application. Simulation experiments are performed to demonstrate the SEA control performance on position tracking, external force estimation, and stiffness tracking. The results confirm that the time delay and the amplitude error in these tests are significantly reduced by the proposed method.


title: Vapor H2O2 sterilization as a decontamination method for the reuse of N95 respirators in the COVID-19 emergency

text: There are a variety of methods routinely used in the sterilization of medical devices using hydrogen peroxide (H2O2) including vaporization, plasma generation and ionization. Many of these systems are used for sterilization and are validated for bioburden reduction using bacterial spores. Here, we explored the benefits of using vaporized H2O2 (VHP) treatment of N95 respirators for emergency decontamination and reuse to alleviate PPE shortages for healthcare workers in the COVID-19 emergency. The factors that are considered for the effective reuse of these respirators are the fit, the filter efficiency and the decontamination/disinfection level for SARS-CoV-2, which is the causative virus for COVID-19 and other organisms of concern in the hospital environment such as methicillin-resistant Staphylococcus aureus or Clostridium difficile. WE showed that the method did not affect fit or filter efficiency at least for one cycle and resulted in a >6 log reduction in bacterial spores and >3.8 log reduction in the infectious SARS-CoV2 load on N95 respirators.


title: Multi-Stage Group Testing Improves Efficiency of Large-Scale COVID-19 Screening

text: Background: SARS-CoV-2 test kits are in critical shortage in many countries. This limits large-scale population testing and hinders the effort to identify and isolate infected individuals. Objectives: Herein, we developed and evaluated multi-stage group testing schemes that test samples in groups of various pool sizes in multiple stages. Through this approach, groups of negative samples can be eliminated with a single test, avoiding the need for individual testing and achieving considerable savings of resources. Study design: We designed and parameterized various multi-stage testing schemes and compared their efficiency at different prevalence rates using computer simulations. Results: We found that three-stage testing schemes with pool sizes of maximum 16 samples can test up to three and seven times as many individuals with the same number of test kits for prevalence rates of around 5% and 1%, respectively. We propose an adaptive approach, where the optimal testing scheme is selected based on the expected prevalence rate. Conclusion: These group testing schemes could lead to a major reduction in the number of testing kits required and help improve large-scale population testing in general and in the context of the current COVID-19 pandemic.


title: The role of children in the spread of COVID-19: Using household data from Bnei Brak, Israel, to estimate the relative susceptibility and infectivity of children

text: One of the significant unanswered questions about COVID-19 epidemiology relates to the role of children in transmission. In this study we estimate susceptibility and infectivity of children compared to those of adults. Understanding the age-structured transmission dynamics of the outbreak provides precious and timely information to guide epidemic modelling and public health policy. Data were collected from households in the city of Bnei Brak, Israel, in which all household members were tested for COVID-19 using PCR. To estimate relative transmission parameters in the absence of data on who infected whom, we developed an estimation method based on a discrete stochastic dynamic model of the spread of the epidemic within a household. The model describes the propagation of the disease between household members allowing for susceptibility and infectivity parameters to vary among two age groups. The parameter estimates are obtained by a maximum likelihood method, where the likelihood function is computed based on the stochastic model via simulations. Inspection of the data reveals that children are less likely to become infected compared to adults (25% of children infected over all households, 44% of adults infected over all households, excluding index cases), and the chances of becoming infected increases with age. An interesting exception is that infants up to age one year are more likely to be infected than children between one and four. Using our modelling approach, we estimate that the susceptibility of children (under 20 years old) is 45% [40%, 55%] of the susceptibility of adults. The infectivity of children was estimated to be 85% [65%,110%] relative to that of adults. It is widely observed that the percentage of children within confirmed cases is low. A common explanation is that children who are infected are less likely to develop symptoms than adults, and thus are less likely to be tested. We estimate that children are less susceptible to infection, which is an additional factor explaining their relatively low rate of occurrence within confirmed cases. Moreover, our results indicate that children, when infected, are somewhat less prone to infect others compared to adults; however, this result is not statistically significant. The resulting estimates of susceptibility and infectivity of children compared to adults are crucial for deciding on appropriate interventions, and for controlling the epidemic outbreak and its progress. These estimates can guide age-dependent public health policy such as school closure and opening. However, while our estimates of children's susceptibility and infectivity are lower than those of adults within a household, it is important to bear in mind that their role in the spread of COVID-19 outside the household, is also affected by different contact patterns and hygiene habits.


title: Deaths from Covid-19: Who are the forgotten victims?

text: Background: With the spreading global pandemic of coronavirus disease 2019 (Covid-19) there has been disruption to normal clinical activity in response to the increased demand on health services. There are reports of a reduction in non-Covid-19 emergency presentations. Consequentially, there are concerns that deaths from non-Covid-19 causes could increase. We examined recent reported population-based mortality rates, compared with expected rates, and compared any excess in deaths with the number of deaths attributed to Covid-19. Methods: National agency and death registration reports were searched for numbers of deaths attributed to Covid-19 and overall mortality that had been publicly reported by 16 April 2020. Data on the number of deaths attributed to Covid-19, the total number of deaths registered in the population and the historical average over at least 3 years were collected. Data were available for 3 Northern European countries (England & Wales, Scotland and the Netherlands) and New York State, United States of America. Results: There was an increase in observed, compared with expected, mortality in Scotland (+27%), England and Wales (+35%), the Netherlands (+60%) and New York state (+26%). Of these deaths, only 43% in Scotland and England and Wales, 49% in the Netherlands and 30% in New York state were attributed to Covid-19 leaving a number of excess deaths not attributed to Covid-19. Conclusions: A substantial proportion of excess deaths observed during the current COVID-19 pandemic are not attributed to COVID-19 and may represent an excess of deaths due to other causes.


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title: Would everyone wearing face masks help us slow the pandemic?

text: As cases of coronavirus disease 2019 (COVID-19) ballooned last month, people in Europe and North America scrambled to get their hands on surgical masks to protect themselves Health officials jumped in to discourage them, worried about the limited supply of masks for health care personnel “Seriously people-STOP BUYING MASKS!” began a 29 February tweet from U S Surgeon General Jerome Adams The World Health Organization and U S Centers for Disease Control and Prevention (CDC) have both said that only people with COVID-19 symptoms and those caring for them should wear masks But some health experts, including the director of the Chinese Center for Disease Control and Prevention, think that’s a mistake Health authorities in parts of Asia have encouraged all citizens to wear masks in public to prevent the spread of the virus, regardless of whether they have symptoms And the Czech Republic took the uncommon step last week of making nose and mouth coverings mandatory in public spaces, prompting a grassroots drive to hand make masks


title: Anxiety levels among Iranian health care workers during the COVID-19 surge: A cross-sectional study

text: The recent surge in COVID-19 cases has exposed health care workers (HCWs) to a wide range of psychological stressors and predisposed them to anxiety-related disorders. Here, we investigated the anxiety level in this population. This multi-center, cross-sectional study was performed on 1038 HCWs in 14 hospitals during the COVID-19 pandemic. Beck anxiety inventory (BAI) was used to measure the level of anxiety in this population. In all, 1038 hospital staffs with a mean age of 36.30+/-8.23 years old participated in this study. Most participants were 31 to 40 years old (43.2), female (87.6%), and nurses (49.5%). The BAI scores for the participants were in a positive skew distribution, with a score range of 0-63, a median of 12 and a mean value of 15.30+/-11.43. Of the 1038 hospital staff, 411 (39.6%) had moderate to severe anxiety. The anxiety level was significantly higher in health care workers [≤]40 years old, women, and nurses. Gender, age, and working positions had the most relation with anxiety, respectively. It seems that HCWs experienced a high level of anxiety in the COVID-19 outbreak. One of the important measures in each epidemic is doing supportive care to maintain the mental well-being of HCWs, especially in higher risk groups, including younger HCWs, women, and nurses.


PlastiCorona: who cares about that waste?


title: Next generation of anti-PD-L1 Atezolizumab with better anti-tumor efficacy in vivo

text: Some cancer patients treated with Atezolizumab, PD-L1 antibody drug launched by Genentech, quickly developed anti-drug antibody (ADA), led to loss of efficacy. This was likely due to the heavy aggregation of Atezolizumab, caused by mutation of N297A for removing unwanted antibody-dependent cytotoxicity (ADCC) of IgG1 antibody drug. Here, we developed a new version of Atezolizumab (Maxatezo), which was demonstrated better anti-tumor efficacy in vivo. In Atezolizumab, we mutated 297A to 297N back to bring back the glycosylation, and inserted a short sequence GGGS between G237 and G238 in the hinge region of the IgG1 heavy chain. Our data shown that insertion of GGGS, without altering the anti-PD-L1 antibody affinity and inhibitory activity, completely abolished the ADCC activity, as same as Atezolizumab. Moreover, the insertion of GGGS, without altering the glycosylation profile of IgG1, increased the yields of anti-PD-L1 antibody considerately. Additionally, glycosylation improved the stability yet reduced the amounts of aggregations in the antibody solutions. In turn, the level of ADA in animals treated with Maxatezo was 70% lower than the ones treated with Atezolizumab. Most importantly, at the same 10mg/kg dose, the anti-tumor activity of Maxatezo had attained 98% compared to that of Atezolizumab at 68%.


title: Index for Volume III

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